RESUMO
INTRODUCTION: Collagenous gastritis (CG), a rare disorder of unknown etiology, has been postulated to have immune-mediated mechanisms. We investigated (i) the incidence and prevalence of CG in a pediatric population; (ii) the clinical, endoscopic, and histologic characteristics of childhood-onset CG; and (iii) the evidence for autoimmunity and/or inflammatory activity in these patients. METHODS: Clinical, endoscopic, and histologic data were reviewed longitudinally in a population-based Swedish cohort of 15 patients with childhood-onset CG diagnosed in the period 2008-2019. A set of 11 autoantibodies, 4 blood inflammatory biomarkers, and the human leukocyte antigen DQ2/DQ8 genotype was analyzed cross-sectionally. RESULTS: The incidence rate of childhood-onset CG was 0.25/100,000 person-years, with an incidence rate ratio of girls to boys of 4.2 (95% confidence interval, 1.2-15). The prevalence of CG was 2.1/100,000 in children aged younger than 18 years. The endoscopic and histologic findings remained pathologic in all the examined patients during a median follow-up of 4.4 years. Many patients had heredity for autoimmune disorders (47%) and/or tested positive for autoantibodies (40%) or human leukocyte antigen DQ2/DQ8 (53%). No associated autoimmune comorbidities were observed. The serum levels of calprotectin and amyloid A were increased in 10/15 (67%) and 5/15 (33%) of the patients, respectively, whereas plasma C-reactive protein levels were normal in all, but 1 patient. DISCUSSION: The results indicate that childhood-onset CG is rare and has a chronic disease course. Although signs of autoimmune predisposition are frequent, early development of autoimmune comorbidities seems seldom. Serum calprotectin and amyloid A represent novel candidate biomarkers of inflammatory activity in CG (see Visual Abstract, Supplementary Digital Content 4, http://links.lww.com/CTG/A349).
Assuntos
Autoanticorpos/sangue , Colágeno/metabolismo , Mucosa Gástrica/patologia , Gastrite/epidemiologia , Adolescente , Idade de Início , Autoanticorpos/imunologia , Biomarcadores/sangue , Biópsia , Proteína C-Reativa/análise , Criança , Estudos de Coortes , Estudos Transversais , Feminino , Mucosa Gástrica/imunologia , Gastrite/sangue , Gastrite/imunologia , Gastrite/patologia , Antígenos HLA-DQ/sangue , Antígenos HLA-DQ/imunologia , Humanos , Incidência , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/imunologia , Complexo Antígeno L1 Leucocitário/sangue , Masculino , Proteína Amiloide A Sérica/análise , Adulto JovemRESUMO
Spleen qi deficiency (SQD) syndrome is one of the basic traditional Chinese medicine (TCM) syndromes related to various diseases including chronic inflammation and hypertension and guides the use of many herbal formulae. However, the biological basis of SQD syndrome has not been clearly elucidated due to the lack of appropriate methodologies. Here, we propose a network pharmacology strategy integrating computational, clinical, and experimental investigation to study the biological basis of SQD syndrome. From computational aspects, we used a powerful disease gene prediction algorithm to predict the SQD syndrome biomolecular network which is significantly enriched in biological functions including immune regulation, oxidative stress, and lipid metabolism. From clinical aspects, SQD syndrome is involved in both the local and holistic disorders, that is, the digestive diseases and the whole body's dysfunctions. We, respectively, investigate SQD syndrome-related digestive diseases including chronic gastritis and irritable bowel syndrome and the whole body's dysfunctions such as chronic fatigue syndrome and hypertension. We found innate immune and oxidative stress modules of SQD syndrome biomolecular network dysfunction in chronic gastritis patients and irritable bowel syndrome patients. Lymphocyte modules were downregulated in chronic fatigue syndrome patients and hypertension patients. From experimental aspects, network pharmacology analysis suggested that targets of Radix Astragali and other four herbs commonly used for SQD syndrome are significantly enriched in the SQD syndrome biomolecular network. Experiments further validated that Radix Astragali ingredients promoted immune modules such as macrophage proliferation and lymphocyte proliferation. These findings indicate that the biological basis of SQD syndrome is closely related to insufficient immune response including decreased macrophage activity and reduced lymphocyte proliferation. This study not only demonstrates the potential biological basis of SQD syndrome but also provides a novel strategy for exploring relevant molecular mechanisms of disease-syndrome-herb from the network pharmacology perspective.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Qi , Baço/patologia , Animais , Doença Crônica , Síndrome de Fadiga Crônica/genética , Síndrome de Fadiga Crônica/imunologia , Gastrite/genética , Gastrite/imunologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hipertensão/genética , Hipertensão/imunologia , Síndrome do Intestino Irritável/genética , Síndrome do Intestino Irritável/imunologia , Linfócitos/imunologia , Camundongos , Fenótipo , Mapas de Interação de Proteínas/efeitos dos fármacos , Células RAW 264.7 , Reprodutibilidade dos Testes , Transdução de Sinais/efeitos dos fármacos , Baço/efeitos dos fármacos , Baço/imunologia , Síndrome , Transcrição Gênica/efeitos dos fármacosRESUMO
A 68-year-old woman presented with a 2-year history of worsening unsteady gait. Her neurological examination revealed peripheral neuropathy with lower limb sensory dominance. T2-weighted imaging revealed a disorder of the posterior cervical cord. Blood test findings revealed vitamin B12 deficiency, and gastroscopy revealed typical findings of autoimmune gastritis. She received vitamin B12 supplementation, but some peripheral neuropathy symptoms persisted due to longstanding vitamin B12 deficiency. Asymptomatic patients should undergo gastroscopy to detect autoimmune gastritis, as chronic vitamin B12 deficiency causes irreversible peripheral neuropathy.
Assuntos
Doenças Autoimunes/complicações , Gastrite/complicações , Gastrite/imunologia , Doenças do Sistema Nervoso Periférico/etiologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Degeneração Combinada Subaguda/etiologia , Degeneração Combinada Subaguda/fisiopatologia , Deficiência de Vitamina B 12/fisiopatologia , Idoso , Feminino , Humanos , Japão , Degeneração Combinada Subaguda/diagnóstico por imagem , Deficiência de Vitamina B 12/sangueRESUMO
Gastritis is a widely spread inflammatory disease, mostly caused by Helicobacter pylori infection. Release of IL-8 by the stomach epithelium is a hallmark of gastritis and contributes to the amplification of the inflammatory state. Pharmacological modulation of IL-8 release is a strategy to relieve gastric inflammation and prevent more severe clinical outcomes. In search of nutraceuticals with potential anti-gastritis properties we used a bio-guided approach based on IL-8 secretion by gastric cells to characterize extracts from the fruits of different chestnut varieties. We found that the ability to inhibit IL-8 secretion correlated with the amount of proanthocyanidins and was associated to the not edible parts of chestnut in all the tested varieties. We also found that the anti-inflammatory activity is preserved upon mild thermal treatment and after in vitro simulated gastric digestion. By combining a robust bio-guided approach with a comprehensive analysis of the tannin fraction of chestnut extracts, we provide evidence for the potential use of chestnut-based nutraceuticals in human gastritis. The bioactive components of chestnut fruits inhibit IL-8 secretion by impairing NF-κB signaling and by other mechanisms, thus opening new applications of proanthocyanidins for inflammation-based diseases.
Assuntos
Aesculus/química , Anti-Inflamatórios/farmacologia , Bioensaio/métodos , Suplementos Nutricionais , Mucosa Gástrica/efeitos dos fármacos , Gastrite/tratamento farmacológico , Extratos Vegetais/farmacologia , Proantocianidinas/farmacologia , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Frutas , Mucosa Gástrica/imunologia , Mucosa Gástrica/metabolismo , Gastrite/imunologia , Gastrite/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-8/metabolismo , Extratos Vegetais/isolamento & purificação , Proantocianidinas/isolamento & purificação , Via SecretóriaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Barks of Ximenia americana are used by the population to treat gastrointestinal inflammatory disorders. Indomethacin is a non-selective non-steroidal anti-inflammatory drug that induces marked gastrointestinal damage. AIMS OF THE STUDIES: To evaluate the gastroprotective activity of total polysaccharides contained in the extract (TPL-Xa) or tea (Tea-Xa) of Ximenia americana barks in the mice gastric damage induced by indomethacin. MATERIALS AND METHODS: TPL-Xa was obtained by a combination of NaOH extraction and ethanol precipitation. Tea-Xa was prepared in distilled water boiled during 5â¯min. Animals received p.o. 0.9% NaCl (saline - control group), TPL-Xa (1-90â¯mg/kg) or Tea-Xa 1â¯h before gastritis induction by indomethacin (20â¯mg/kg). Mice were sacrificed 7â¯h after gastritis induction and analyzed for the following parameters: stomach lesions measurement; histological evaluation; myeloperoxidase (MPO) activity; nitrate/nitrite and cytokine levels; leukocyte adhesion and rolling by intravital microscopy. RESULTS: TPL-Xa reduced macroscopic and microscopic damage, MPO activity (59%), leukocyte rolling (86%) and adhesion (84%), nitrite/nitrate ratio (100%) and IL-8 (69%), but increased IL-4 (50%). Tea-Xa (12.8 yield; 39.3% carbohydrate, including 25.8% uronic acid; 4% protein) reduced macroscopic damage (62%) and MPO activity (50%). CONCLUSION: TPL and Tea of Ximenia americana barks ameliorate the gastric injury induced by indomethacin in mice, an effect that was dependent on the reduction of neutrophil infiltration.
Assuntos
Bebidas , Gastrite/tratamento farmacológico , Olacaceae , Extratos Vegetais , Polissacarídeos , Substâncias Protetoras , Animais , Anti-Inflamatórios não Esteroides , Adesão Celular/efeitos dos fármacos , Feminino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/imunologia , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Gastrite/induzido quimicamente , Gastrite/imunologia , Gastrite/metabolismo , Indometacina , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Migração e Rolagem de Leucócitos/efeitos dos fármacos , Leucócitos/efeitos dos fármacos , Leucócitos/fisiologia , Camundongos , Infiltração de Neutrófilos/efeitos dos fármacos , Nitratos/metabolismo , Nitritos/metabolismo , Peroxidase/metabolismo , Fitoterapia , Casca de Planta , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêuticoRESUMO
Berberine (BBR) is an isoquinoline alkaloid derived from various medicinal herbs. Previous studies have suggested that BBR exerts antimicrobial, antitumor, and antidiabetic effects and can be used to treat Helicobacter pylori-induced chronic gastritis. However, the exact mechanism by which BBR inhibits H. pylori infection is not fully understood. We investigated the anti-inflammatory properties and potential mechanism of BBR in H. pylori-infected mice with chronic gastritis. We found that BBR can suppress the expression of pro-inflammatory genes IL-6, TGF-ß, and IL-1ß and upregulate anti-inflammatory gene IL-10 expression in the mucosa and RAW 264.7 macrophages. Exposure to BBR also reduced the expression and accumulation of IL-17 in the mucosa and CD4+ T cells activated by anti-CD3 and anti-CD28, and it decreased the frequency of IL-17-producing CD4+ T cells. B cell-activating factor (BAFF) production was inhibited by BBR and by cultured dendritic and CD4+ T cells. Furthermore, we demonstrated that BAFF can trigger the Th17 response by promoting the production of pro-Th17 cytokines IL-6, TGF-ß, and IL-1ß, which are strongly associated with the anti-inflammatory role of BBR in chronic gastritis caused by H. pylori. In conclusion, we determined that BBR has anti-inflammatory effects on H. pylori-induced chronic gastritis by attenuating the BAFF-triggered Th17 response.
Assuntos
Anti-Inflamatórios/farmacologia , Fator Ativador de Células B/metabolismo , Berberina/farmacologia , Gastrite/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Células Th17/imunologia , Animais , Fator Ativador de Células B/genética , Células Cultivadas , Doença Crônica , Citocinas/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/imunologia , Mucosa Gástrica/microbiologia , Gastrite/imunologia , Gastrite/microbiologia , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/microbiologia , Interleucina-17/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células Th17/efeitos dos fármacos , Células Th17/microbiologiaRESUMO
How the immune system maintains peripheral tolerance under inflammatory conditions is poorly understood. Here we assessed the fate of gastritogenic T cells following inflammatory activation in vivo. Self-reactive T cells (A23 T cells) specific for the gastric H+ /K+ ATPase α subunit (HKα) were transferred into immunosufficient recipient mice and immunised at a site distant to the stomach with adjuvant containing the cognate HKα peptide antigen. Activation of A23 T cells by immunisation did not impact on either immune tolerance or protection from gastric autoimmunity in wild-type BALB/c mice. However, increased presentation of endogenously derived HKα epitopes by dendritic cells (DCs) in the gastric lymph node of IE-H+ /K+ ß transgenic mice (IEß) reduces A23 T-cell tolerance to gastric antigens after inflammatory activation, with subsequent development of gastritis. While HKα-specific A23 T cells from immunised wild-type mice were poorly responsive to in vitro antigen specific activation, A23 T cells from immunised IEß transgenic mice were readily re-activated, indicating loss of T-cell anergy. These findings show that DCs of gastric lymph nodes can maintain tolerance of pathogenic T cells following inflammatory stimulation and that the density of endogenous antigen presented to self-reactive T cells is critical in the balance between tolerance and autoimmunity.
Assuntos
Apresentação de Antígeno , Autoantígenos/imunologia , Autoimunidade , Suscetibilidade a Doenças , Gastrite/imunologia , Animais , Biomarcadores , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Sobrevivência Celular/genética , Sobrevivência Celular/imunologia , Anergia Clonal/genética , Anergia Clonal/imunologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Gastrite/metabolismo , Gastrite/patologia , ATPase Trocadora de Hidrogênio-Potássio/genética , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Imunofenotipagem , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Fenótipo , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismoRESUMO
In the present study we chemically profiled tannin-enriched extracts from strawberries and tested their biological properties in a cell model of gastric inflammation. The chemical and biological features of strawberry tannins after in vitro simulated gastric digestion were investigated as well. The anti-inflammatory activities of pure strawberry tannins were assayed to get mechanistic insights. Tannin-enriched extracts from strawberries inhibit IL-8 secretion in TNFα-treated human gastric epithelial cells by dampening the NF-κB signaling. In vitro simulated gastric digestion slightly affected the chemical composition and the biological properties of strawberry tannins. By using pure compounds, we found that casuarictin may act as a pure NF-κB inhibitor while agrimoniin inhibits IL-8 secretion also acting on other biological targets; in our system procyanidin B1 prevents the TNFα-induced effects without interfering with the NF-κB pathway. We conclude that strawberry tannins, even after in vitro simulated gastric digestion, exert anti-inflammatory activities at nutritionally relevant concentrations.
Assuntos
Anti-Inflamatórios/farmacologia , Células Epiteliais/efeitos dos fármacos , Fragaria/química , Mucosa Gástrica/efeitos dos fármacos , Gastrite/prevenção & controle , Interleucina-8/metabolismo , Extratos Vegetais/farmacologia , Taninos/farmacologia , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Mucosa Gástrica/imunologia , Mucosa Gástrica/metabolismo , Gastrite/genética , Gastrite/imunologia , Gastrite/metabolismo , Humanos , Interleucina-8/genética , Interleucina-8/imunologia , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , NF-kappa B/metabolismo , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Regiões Promotoras Genéticas , Transdução de Sinais/efeitos dos fármacos , Taninos/isolamento & purificação , Transfecção , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
Helicobocterpylori (HP) - the human infection that persists for a long time in the stomach and can cause chronic gastritis, gastric and duodenal ulcer, MALT-lymphoma, gastric adenocarcinoma. There is a well-adapted niche-specific microbial community in the stomach represented by Lactobocillus, Streptococcus ahd other bacteria. Use of probiotics is considered to be an alternative or supplement to eradication therapy Among the Lactobacillus the most promising is Loctobocillus reutert who are able to have the anti-HP activity L. reureri produces powerful antimicrobial compounds such as reuterin, reuteritsin 6, reutetsiklin and metabolites that inhibit the growth of I-/P (volatile fatty acids, lactic acid, hydrogen peroxide, etc.). These compounds could reduce the adhesion of HP to gastric epithelial cells, inhibit growth HP, which leads to a significant reduction in the degree of contamination of HP and the severity of gastric mucosal inflammation. The data on the effectiveness of L. re uteri as monotherapy in patients with HP without absolute indications for eradication, and as an additional component, which increase the effectiveness of eradication are presented.
Assuntos
Adenocarcinoma , Úlcera Duodenal , Gastrite , Infecções por Helicobacter , Helicobacter pylori/imunologia , Limosilactobacillus reuteri/imunologia , Linfoma de Zona Marginal Tipo Células B , Neoplasias Gástricas , Adenocarcinoma/imunologia , Adenocarcinoma/microbiologia , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Úlcera Duodenal/imunologia , Úlcera Duodenal/microbiologia , Úlcera Duodenal/patologia , Úlcera Duodenal/terapia , Gastrite/imunologia , Gastrite/microbiologia , Gastrite/patologia , Gastrite/terapia , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/patologia , Infecções por Helicobacter/terapia , Humanos , Linfoma de Zona Marginal Tipo Células B/imunologia , Linfoma de Zona Marginal Tipo Células B/microbiologia , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma de Zona Marginal Tipo Células B/terapia , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/terapiaRESUMO
INTRODUCTION: The development of the intestinal gut is largely influenced by early nutrition. Infant immunity is challenged by the exposure of the gut to foreign bodies, which mediate inflammation of the gut. This study assessed the levels of gut inflammation in relation to the percentage of breastmilk consumed/the exclusivity of breastfeeding in South African infants. This is the first study to examine markers of gut inflammation in infants in relation to exclusivity of breastfeeding measured by a gold standard method. METHODOLOGY: Twenty-four black South African infants were included in this study. The categorization of different degrees of exclusivity of breastfeeding was made using an objective gold standard method developed by the International Atomic Energy Agency (deuterium dilution method). Markers of gut inflammation were measured noninvasively by sampling stool from the infants averaging 6 months of age. Gut inflammation was investigated by running multiple Droplet Digital™ (Bio-Rad, Hercules, CA) polymerization chain reaction tests profiling a panel of five mRNA probes (interleukin-8 [IL-8], S100 calcium-binding protein A8 [S100A8], Toll-like receptor-4, human leukocyte antigen on chromosome 6 region 6p21.31, and defensin alpha 8). These mRNA biomarkers expressions were tested in proportion to number of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) copies as GAPDH is constitutively expressed in most cells. RESULTS: Two previously described robust mRNA markers of gut inflammation (S100A8 and IL-8) were found to correlate significantly to the percentage of breastmilk intake (r(2) = 0.4302, p = 0.0004 and r(2) = 0.3633, p = 0.002, respectively) in the range of 75-100% in 22 samples analyzed. CONCLUSIONS: This study using objective methodology has shown that higher percentages of breastmilk intake are associated with significantly lower levels of gut inflammation. This further supports the health benefits observed in exclusively breastfed infants.
Assuntos
Aleitamento Materno , Disbiose/prevenção & controle , Gastrite/prevenção & controle , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Leite Humano/imunologia , Imunidade Adaptativa , Adulto , Biomarcadores/metabolismo , Disbiose/imunologia , Feminino , Gastrite/imunologia , Humanos , Imunidade Inata , Imunidade nas Mucosas , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente/imunologia , Recém-Nascido , MasculinoRESUMO
OBJECTIVE: To explore the immune mechanism of moxibustion on protecting gastric mucosa injury. METHODS: Forty healthy SD rats were randomly divided into four groups: a blank group, a model group, a moxibustion acupoint group and a moxibustion non-acupoint group, 10 rats in each one. Eight days before model establishment, moxibustion at "Zusanli" (ST 36), "Zhongwan" (CV 12), "Guanyuan" (CV 4), "Pishu" (BL 20) and "Weishu" (BL 21) was applied in the moxibustion acupoint group while these acupoints' controlled points were selected in the moxibustion non-acupoint group, and no treatment was given in the model group, once a day in three groups for continuous 16 days. The helicobacter pylori (Hp) model was established by intragastric administration of Hp. HE staining microscopic examination was used to observe inflammation severity in gastric mucosa, and enzyme-linked immunosorbent assay (ELISA) was adapted to measure content of heat shock protein (HSP) 72, TNF-alpha and IL-1beta, and real-time quantitative PCR was used to measure the expression of TLR2 mRNA, TLR4 mRNA, CD14 mRNA and MyD88 mRNA in peripheral blood mononuclear cells, and western blot method was used to measure content of NFkappaB and IkappaBalpha in peripheral blood mononuclear cells. RESULTS: Compared with the blank group, the expression of HP could be seen in the smear of gastric mucosa by Gram's staining in the model group; the inflammation severity score was obviously increased as well as content of serum HSP 72 and TNF-alpha and IL-1beta in gastric tissue; and expression of TLR2, 4 mRNA, CD14 mRNA, MyD88 mRNA, NFkappaB was increased (P < 0.01), but the expression of IkappaBalpha was reduced (P < 0.05). After the moxibustion, the inflammation severity score was reduced in the moxibustion acupoint group, and the content of serum HSP 72 was increased, and the expression of TNF-alpha and IL-1beta in gastric tissue and expression of TLR2 mRNA, TLR4 mRNA, CD14 mRNA, MyD88 mRNA and NFkappaB were reduced (P < 0.01), but the expression of IkappaBalpha was increased (P < 0.05). The differences between the moxibustion non-acupoint group and the model group were not significant (P > 0.05). CONCLUSION: The pretreatment of moxibustion at acupoints could induce the over expression of serum HSP 72. By combining TLR 2 and 4 receptors to trigger receptor signal transduction pathways, the releases of downstream signal substances are regulated; as a result, the releases of related immune substances are regulated to relieve the gastric mucosa injury of rats with HP gastritis.
Assuntos
Gastrite/imunologia , Gastrite/terapia , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/terapia , Moxibustão , Pontos de Acupuntura , Animais , Feminino , Infecções por Helicobacter/genética , Helicobacter pylori/fisiologia , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Masculino , NF-kappa B/genética , NF-kappa B/imunologia , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Autoimmune gastritis is an organ-specific autoimmune disease of the stomach associated with pernicious anemia. The previous work from us and other groups identified MCPIP1 as an essential factor controlling inflammation and immune homeostasis. MCPIP1(-/-) developed severe anemia. However, the mechanisms underlying this phenotype remain unclear. In the present study, we found that MCPIP1 deficiency in mice resulted in severe anemia related to autoimmune mechanisms. Although MCPIP1 deficiency did not affect erythropoiesis per se, the erythropoiesis in MCPIP1(-/-) bone marrow erythroblasts was significantly attenuated due to iron and vitamin B12 (VB12) deficiency, which was mainly resulted from autoimmunity-associated gastritis and parietal cell loss. Consistently, exogenous supplement of iron and VB12 greatly improved the anemia phenotype of MCPIP1(-/-) mice. Finally, we have evidence suggesting that autoimmune hemolysis may also contribute to anemia phenotype of MCPIP1(-/-) mice. Taken together, our study suggests that MCPIP1 deficiency in mice leads to the development of autoimmune gastritis and pernicious anemia. Thus, MCPIP1(-/-) mice may be a good mouse model for investigating the pathogenesis of pernicious anemia and testing the efficacy of some potential drugs for treatment of this disease.
Assuntos
Anemia/genética , Anemia/imunologia , Ribonucleases/deficiência , Anemia/metabolismo , Anemia/patologia , Anemia Ferropriva/genética , Anemia Ferropriva/imunologia , Anemia Ferropriva/metabolismo , Animais , Autoanticorpos/imunologia , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Medula Óssea/patologia , Modelos Animais de Doenças , Eritrócitos/imunologia , Eritropoese/genética , Gastrite/genética , Gastrite/imunologia , Gastrite/patologia , Estudos de Associação Genética , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Knockout , Células Parietais Gástricas/metabolismo , Células Parietais Gástricas/patologia , Ribonucleases/genética , Ribonucleases/metabolismo , Baço/metabolismo , Baço/patologia , Deficiência de Vitamina B 12RESUMO
AIM: To study effect of diterpenoid C extracted from radix curcumae on Helicobacter pylori (H. pylori)-infected inflammation, intestinal metaplasia, and nuclear factor kappa B (NF-κB) signaling pathway in vitro. METHODS: We used I-type H. pylori to infect human gastric epithelial gastric epithelium cell line (GES-1) cell lines, and then H. pylori-infected GES-1 cells were treated with radix curcumae (RC)-derived diterpenoid C of different concentrations (5, 10, 20 µg/mL) and amoxicillin. The expression of p65, IκB kinase (IKK) α and IKKγ proteins was detected with Western blotting, and the expression of interleukin (IL)-8, IL-6 and IL-4 was determined with enzyme-linked immunosorbent assay method. Data were analyzed using SPSS software ver18.0. For comparisons between groups of more than two unpaired values, one-way analysis of variance (ANOVA) was used. If an ANOVA F value was significant, post hoc comparisons were performed between groups. If results were not normally distributed, the Mann-Whitney U test was used to compare two groups of unpaired values, whereas for comparisons between groups of more than two unpaired values, the Kruskal-Wallis H test was used. Statistical significance was established at P < 0.05. RESULTS: The MTT assay results revealed the inhibited rate of GES-1, and indicated that the IC5 of RC-derived diterpenoid C and amoxicillin all were 5 µg/mL for gastric GES-1 cells. The expression of IL-8 was significantly increased, especially at 12 h time point; and the expression of IL-4 was decreased in H. pylori-infected GES-1 cells. After H. pylori-infected GES-1 cells were treated with RC-derived diterpenoid C of different concentrations and amoxicillin, the expression of IL-8 was decreased at 12, 24, 48, 72 h points (P < 0.01), especially in high-concentration diterpenoid C (20 µg/mL) group; and the expression of IL-4 was increased, especially in moderate and high-concentration diterpenoid C (10 and 20 µg/mL) groups. RC-derived diterpenoid C had the inhibitory effects on H. pylori-induced p65 translocation from cytoplasm into cell nucleus, H. pylori-stimulant IkBα degradation, the phosphorylation of p65 and IkBα, and the expression of IKKα and IKKß proteins. CONCLUSION: RC-derived diterpenoid C can block NF-κB signal pathway, effectively reducing the secretion of H. pylori-induced proinflammatory cytokine and increasing the secretion of anti-inflammatory cytokine.
Assuntos
Anti-Inflamatórios/farmacologia , Curcuma , Diterpenos/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Gastrite/tratamento farmacológico , Helicobacter pylori/patogenicidade , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Curcuma/química , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Mucosa Gástrica/imunologia , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Gastrite/imunologia , Gastrite/metabolismo , Gastrite/microbiologia , Humanos , Quinase I-kappa B/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-4/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Fosforilação , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Rizoma , Fatores de Tempo , Fator de Transcrição RelA/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Dipterocarpus tuberculatus Roxb. (Dipterocarpaceae) has been traditionally used to treat various inflammatory symptoms. However, no mechanistic studies on the anti-inflammatory actions of D. tuberculatus have been reported. This study is therefore aimed at exploring the anti-inflammatory effects of 95% ethanol extracts (Dt-EE) of this plant. MATERIALS AND METHODS: The regulatory activity of Dt-EE and its molecular mechanism on the release of nitric oxide (NO) and prostaglandin (PG)E2 in lipopolysaccharide (LPS)-treated macrophage-like RAW264.7 cells were elucidated by evaluating the activation of transcription factors and their upstream signals and by analyzing the kinase activities of target enzymes. Furthermore, to confirm its availability for oral use, an EtOH/HCl-induced acute gastritis model was tested with this extract. RESULTS: Dt-EE effectively suppressed LPS-mediated inflammatory responses such as the production of NO and PGE2 from macrophages in a dose-dependent manner. In particular, Dt-EE clearly blocked the activation of NF-κB by blocking the phosphorylation of its upstream enzymes IKK and Akt. Using a direct enzyme assay, Dt-EE was shown to block the enzyme activity of PDK1. Finally, this extract also remarkably ameliorated inflammatory lesions in the stomach induced by EtOH/HCl. CONCLUSION: Our data strongly suggest that Dt-EE can be considered as a novel anti-inflammatory remedy with PDK1/NF-κB inhibitory properties and can also be used to treat gastritis symptoms. In addition, our findings can serve as a basis for further phytochemical and pharmacological studies in the future.
Assuntos
Anti-Inflamatórios/uso terapêutico , Dipterocarpaceae/química , Gastrite/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Doença Aguda , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Dinoprostona/antagonistas & inibidores , Dinoprostona/biossíntese , Modelos Animais de Doenças , Etanol/química , Gastrite/induzido quimicamente , Gastrite/imunologia , Células HEK293 , Humanos , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Macrófagos/imunologia , Camundongos , NF-kappa B/antagonistas & inibidores , NF-kappa B/biossíntese , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Folhas de Planta/química , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
OBJECTIVE: To study the correlation between the Th1/Th2 balance in the peripheral blood and Pi-Wei damp-heat syndrome (PDS) in chronic gastritis (CG). METHODS: Fifty-one patients with CG of PDS were recruited, including 22 cases with predominant damp (PDS-D), 9 case with predominant heat (PDS-H), and 20 case with simultaneous onset of damp and Heat (PDS-DH). Besides, 10 healthy volunteers were recruited as the healthy control group. H. pylori (HP) infection was detected by fast urea enzyme, and the expressions of Th1 type cytokines interferon-gamma (IFN-gamma), interleukin-12 (IL-12), and Th2 type cytokines interleukin-4 (IL-4), interleukin-10 (IL-10) in serum were detected by luminex technology. RESULTS: The HP infection rate was 41.18% (21/51) in the PDS patients, obviously higher than that in the healthy control group (10.00%,1/10), showing statistical difference (P<0.05). The HP infection rate was 45.45% (10/22) in PDS-D, 22.22% (2/9) in PDS-H, and 45.00% (9/20) in PDS-DH. The HP infection rate in PDS-D and PDS-DH was significantly higher than that of the healthy control group, showing statistical difference (P<0.05). There was no statistically significant difference in the expressions of peripheral blood IFN-gamma, IL-12, IL-4, and IL-10 between the PDS patient group and the healthy control group (P>0.05). But the expressions of IFN-gamma and IL-12 showed an increasing trend in the PDS patient group, while the expression of IL-4 showed a decreasing trend. The expressions of IFN-gamma, IL-12, IL-4, and the ratios of IFN-gamma/IL-4 and IL-12/IL-4 were also higher in PDS-DH group than in the PDS-D group and the PDS-H group, but with no statistical significance (P>0.05). CONCLUSION: The occurrence of Pi-Wei damp-heat CG was possibly correlated with the imbalance of Th1/Th2. Damp and heat pathogen might be important pathogenic factors leading to Th1 type cytokine immunoreaction.
Assuntos
Gastrite/imunologia , Gastrite/patologia , Equilíbrio Th1-Th2 , Adulto , Estudos de Casos e Controles , Doença Crônica , Citocinas/sangue , Feminino , Gastrite/diagnóstico , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/patologia , Humanos , Masculino , Medicina Tradicional Chinesa/métodos , Células Th1/imunologia , Células Th2/imunologiaRESUMO
BACKGROUND AND AIM: We aimed to evaluate the changes in histopathologic features, concentrations of vitamins C and E in gastric mucosa, and total antioxidant capacity of the body after ingestion of ascorbic acid and alpha tocopherol in patients with Helicobacter pylori. MATERIAL AND METHOD: Patients with H. pylori-positive nonulcer dyspepsia were included in this study. Tissue samples were taken from the lesser and greater curvature in both prepyloric antrum and corpus for histopathologic examination and measurement of vitamins C and E concentrations. Blood samples were obtained for measurement of the total antioxidant capacity of the body. The patients were given vitamin C 500 mg BID and vitamin E 200 IU BID for 4 weeks orally. At the end of the 4th week, the initial procedures were repeated. Histopathologic examination of the tissue samples were carried out by two pathologists. RESULTS: The mean vitamins C and E concentrations in gastric mucosa at the 4th week were higher than those at the beginning (p = .000 and p = .006, respectively). Mean total antioxidant capacity of the body at the beginning and that at the 4th week were similar (p = .689). H. pylori intensity in the antrum at the beginning was higher than that at the 4th week for both pathologists (p = .007 and p = .039). Neutrophilic activity in the antrum at the beginning was higher than that at the 4th week for both pathologists (p = .000 and p = .025). Neutrophilic activity in the corpus at the beginning was higher than that at the 4th week for pathologist 1 (p = .033), and they were similar for pathologist 2 (p = .763). CONCLUSION: The findings that H. pylori intensity and neutrophilic activity decrease through increasing gastric ascorbic acid and alpha tocopherol concentrations suggest that supplementation with vitamins C and E increases the eradication rates via impairing the microenvironment created by the bacteria and facilitating the diffusion of antibiotics into gastric mucosa.
Assuntos
Ácido Ascórbico/administração & dosagem , Gastrite/tratamento farmacológico , Gastrite/patologia , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/patologia , Helicobacter pylori/crescimento & desenvolvimento , alfa-Tocoferol/administração & dosagem , Adulto , Suplementos Nutricionais/análise , Feminino , Gastrite/imunologia , Gastrite/microbiologia , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Humanized murine models comprise a new tool to analyze novel therapeutic strategies for allergic diseases of the intestine. OBJECTIVE: In this study we developed a human PBMC-engrafted murine model of allergen-driven gut inflammation and analyzed the underlying immunologic mechanisms. METHODS: Nonobese diabetic (NOD)-scid-γc(-/-) mice were injected intraperitoneally with human PBMCs from allergic donors together with the respective allergen or not. Three weeks later, mice were challenged with the allergen orally or rectally, and gut inflammation was monitored with a high-resolution video miniendoscopic system, as well as histologically. RESULTS: Using the aeroallergens birch or grass pollen as model allergens and, for some donors, also hazelnut allergen, we show that allergen-specific human IgE in murine sera and allergen-specific proliferation and cytokine production of human CD4(+) T cells recovered from spleens after 3 weeks could only be measured in mice treated with PBMCs plus allergen. Importantly, these mice had the highest endoscopic scores evaluating translucent structure, granularity, fibrin, vascularity, and stool after oral or rectal allergen challenge and a strong histologic inflammation of the colon. Analyzing the underlying mechanisms, we demonstrate that allergen-associated colitis was dependent on IgE, human IgE receptor-expressing effector cells, and the mediators histamine and platelet-activating factor. CONCLUSION: These results demonstrate that allergic gut inflammation can be induced in human PBMC-engrafted mice, allowing the investigation of pathophysiologic mechanisms of allergic diseases of the intestine and evaluation of therapeutic interventions.
Assuntos
Alérgenos/imunologia , Gastrite/imunologia , Hipersensibilidade/imunologia , Imunoglobulina E/imunologia , Leucócitos Mononucleares/transplante , Administração Oral , Administração Retal , Alérgenos/administração & dosagem , Animais , Especificidade de Anticorpos/imunologia , Linfócitos T CD4-Positivos/imunologia , Citocinas/biossíntese , Modelos Animais de Doenças , Gastrite/patologia , Gastrite/prevenção & controle , Antagonistas dos Receptores Histamínicos/metabolismo , Humanos , Hipersensibilidade/patologia , Hipersensibilidade/prevenção & controle , Imunoglobulina E/sangue , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Ativação Linfocitária/imunologia , Camundongos , Camundongos Knockout , Camundongos SCID , Glicoproteínas da Membrana de Plaquetas/antagonistas & inibidores , Pólen/imunologia , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores de IgE/metabolismo , Baço/imunologiaRESUMO
BACKGROUND/AIMS: CJ-20001 is a phytopharmaceutical agent and currently being investigated in a Phase II trial for the treatment of acute and chronic gastritis patients in Korea. In this study we addressed the protective effects of CJ-20001 against water immersion restraint stress (WIRS)-induced gastric injury in rats and studied the underlying mechanisms. METHODOLOGY: To evaluate the protective effect of CJ-20001 on stress-induced gastric lesions, rats were exposed to water immersion restraint stress. Inflammatory infiltration into gastric mucosa was examined by immunohistochemistry and in vitro invasion assay. Expression of proinflammatory cytokines was detected with reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Pretreatment with CJ-20001 dose-dependently attenuated the WIRS-induced gastric lesions as demonstrated by gross pathology and histology. WIRS increased infiltration of mast cells and macrophages into the gastric mucosa and submucosal layer, whereas the inflammatory infiltration was markedly inhibited by CJ-20001 administration. An in vitro cell invasion assay showed that treatment with CJ-20001 decreased the migration of macrophages. CJ-20001 suppressed the expression of proinflammatory cytokines, IL-18, IP-10 and GRO/KC, in lipopolysaccharides (LPS)-treated macrophages. CONCLUSIONS: These data suggest that novel phytopharmaceutical agent CJ-20001 has the potent anti-inflammatory properties through inhibition of inflammatory infiltration in psycho-physiological stress-induced gastric injury.
Assuntos
Anti-Inflamatórios/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Gastrite/prevenção & controle , Fármacos Gastrointestinais/farmacologia , Extratos Vegetais/farmacologia , Preparações de Plantas/farmacologia , Estresse Psicológico/tratamento farmacológico , Animais , Quimiotaxia/efeitos dos fármacos , Citocinas/genética , Citocinas/metabolismo , Citoproteção , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Mucosa Gástrica/imunologia , Mucosa Gástrica/patologia , Gastrite/etiologia , Gastrite/genética , Gastrite/imunologia , Gastrite/patologia , Humanos , Imersão , Imuno-Histoquímica , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Restrição Física , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estresse Psicológico/complicações , Estresse Psicológico/etiologia , Estresse Psicológico/genética , Estresse Psicológico/imunologia , Estresse Psicológico/patologia , Células U937RESUMO
OBJECTIVE: To investigate the effect of Jianpi Yiqi Qingyou decoction on lymphocyte subsets and IL-2 mRNA in gastric tissue in rats with chronic superficial gastritis. METHOD: Wistar rats were randomly divided into 6 groups (11 for each): a blank control groups, the model of the control groups, the treatment groups (low-dose groups of traditional Chinese medicine, moderate-dose groups of traditional Chinese medicine, high-dose groups of traditional Chinese medicine) and lansoprazole groups. The models were made with the method in reference except a blank control groups. These rats are drinking freely with 0. 02% ammonia, continuous 90 days, and made preparations for experimental animal model of superficial gastritis. Making the model were detected by HE dying. The count of CD3+, CD4+ and CD8+ T cells were detected by immunohistochemistry. Using reverse transcriptase polymerase chain reaction (RT-PCR), the expression levels of IL-2 mRNA in gastric tissue were quantified. RESULT: Compared with that in model groups, the content of CD3+ T cells and CD4+ T cells in gastric tissue obviously increased in high dose of traditional Chinese medicine groups , the content of CD8+ T cells in gastric tissue obviously decreased in high dose of traditional Chinese medicine groups and the difference was significant (P < 0.01). The expression levels of IL-2 mRNA in gastric tissue obviously increased in moderate and high doses of traditional Chinese medicine groups, and the difference was significant compared with that in model group (P < 0.01). CONCLUSION: Jianpi Yiqi Qingyou decoction can obviously improve the content of CD3+ T cells and CD4+ T cells and the expression levels of IL-2 mRNA, decrease the content of CD8+ T cells in gastric tissue, improve immunity of rats. So the research results can provide some evidences for the treatment for chronic superficial gastritis.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Gastrite/genética , Gastrite/patologia , Interleucina-2/genética , Estômago/efeitos dos fármacos , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/metabolismo , Animais , Relação CD4-CD8 , Doença Crônica , Feminino , Mucosa Gástrica/metabolismo , Gastrite/imunologia , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estômago/imunologia , Estômago/patologiaRESUMO
OBJECTIVES: We investigated the correlation between Japanese apricot (JA) intake and Helicobacter pylori-related chronic atrophic gastritis (CAG). METHODS: A questionnaire was administered and serum anti-H. pylori IgG antibodies measured in 1358 asymptomatic adults. The subjects were divided into high-intake and low-intake groups. Histological and serological evaluation of H. pylori-related CAG was performed in 68 non-elderly volunteers. RESULTS: The H. pylori-negative rate did not differ significantly between the high-intake and low-intake groups. Mean antibody titers were lower in the high-intake group, but the difference was not significant. There was no significant difference in the rate of H. pylori infection on the basis of JA intake when subjects were stratified by age. Among H. pylori-positive non-elderly subjects, antibody titers were significantly lower in the high-intake group (P=0.041). Endoscopic tissue biopsy from the 68 volunteers showed less H. pylori bacterial load and mononuclear infiltration irrespective of gastric site in the high-intake group. In the high-intake group, antral neutrophil infiltration was significantly less pronounced and corporal atrophy was less extensive. Serological evaluation using serum PG levels also confirmed these histopathological data. CONCLUSIONS: Our findings strongly indicate a preventive effect of JA intake on CAG by inhibiting H. pylori infection and reducing active mucosal inflammation.