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1.
Gene ; 722: 144098, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31494241

RESUMO

This study evaluated the possible association between SNPs in cytokines coding genes, namely IL10, IL6 and IFNG, cytokines serum levels and clinical assessment' scores in patients with Rheumatoid Arthritis(RA). SNPs genotyping was performed in 126 RA patients and 177 healthy individuals with Taqman probes specific for IL10 -1082 (T>C, rs1800896);INFG -1616 (A>G, rs2069705) and IL6 -174 (G>C, rs1800795) variants,positioned in regulatory regions. Cytokine Bead Array (CBA) was used to measure cytokine levels. We found association between INFG -1616 G allele(p = 0.0210; OR = 1.605) and INFG -1616 GG genotype (p = 0.0268; OR =2.609) and RA susceptibility. We also observed association between IL10 -1082 TT genotype and high clinical disease activity index (CDAI) values (p = 0.026; OR = 1.906; 95% CI = 1.082 - 3.359), IL10 -1082 CC genotype and low CDAI values (p = 0.016; OR = 0.256) and INFG -1616 AA and high CDAI values (p = 0.025; OR = 2.919). IL10 -1082 CC also exhibited the lowest IL-10 levels than IL10 -1082 TT (p = 0.020) and IL10 -1082 TC (p = 0.032). Finally, we verified higher IL-6 value in the RA patients than healthy control group (p = 0.007) and an association between high IL-6 levels and increased CDAI (r = 0.4648, p = 0.0015); DAS 28 (r = 0.3933, p= 0.0091), presence of bone erosions (r = 0.3170, p = 0.0361), ESR levels(r = 0.3041, p = 0.0448) and IFN-γ levels (r = 0.3049, p = 0.0468).Altogether, we suggest that IL10 -1082 (T>C, rs1800896) and INFG -1616(A>G, rs2069705) polymorphisms as well as IL-6 levels alterations may play a role for prognostic and disease follow-up.


Assuntos
Artrite Reumatoide/genética , Interferon gama/genética , Interleucina-10/genética , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único , Adulto , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Feminino , Frequência do Gene , Genótipo , Humanos , Interferon gama/sangue , Interleucina-10/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade
2.
Clin Exp Rheumatol ; 37 Suppl 119(4): 76-81, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31587692

RESUMO

OBJECTIVES: Vitamin D status influences the risk to develop autoimmune diseases affecting the percentage and/or functions of regulatory T cells (Tregs). Since low levels of 25 (OH) D have been decreased in patients with systemic sclerosis (SSc), we aimed to study the effect of Vitamin D3 (cholecalciferol) supplementation on Tregs frequencies and functions. METHODS: Peripheral blood and sera samples were obtained from 45 SSc patients and controls (HC). A number of eighteen SSc patients had consumed Cholecalciferol (orally) at the dose of 25.000 UI/month for 6 months at the time of enrollment. 25(OH)D serum levels were measured and VDR polymorphisms, were genotyped by polymerase chain reaction (PCR). Tregs isolated from peripheral blood mononuclear cells were in vitro expanded and a suppression assay was performed. Flow cytometry analysis was then carried out. Finally, IL-10 production was assayed by ELISA. RESULTS: Low serum levels of 25(OH)D were detected in SSc patients. The percentage of Tregs in SSc patients was similar to controls, but, among SSc patients, it was higher in those patients taking cholecalciferol. Tregs capability to suppress T cell proliferation was impaired in SSc patients and not restored after in vitro pre-treatment with the active form of Vitamin D (1,25(OH)2D3); but at the same time the production of IL-10 was increased in treated samples obtained from patients. The lack of response of Tregs from SSc patients to 1,25(OH)2D3 treatment in vitro was not due to altered Vitamin D/VDR signalling. CONCLUSIONS: Altogether, our results indicate that the increased production of IL-10 by 1,25(OH)2D3 -treated Tregs could provide a "suppressive" cytokine milieu able to modulate immune response but it is not sufficient to restore the immune suppressive functions of Tregs.


Assuntos
Interleucina-10/biossíntese , Escleroderma Sistêmico , Linfócitos T Reguladores/efeitos dos fármacos , Vitamina D , Estudos de Casos e Controles , Suplementos Nutricionais , Feminino , Humanos , Leucócitos Mononucleares , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/metabolismo , Vitamina D/farmacologia
3.
Adv Exp Med Biol ; 1172: 79-96, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31628652

RESUMO

The Interleukin (IL)-10 cytokine family includes IL-10, IL-19, IL-20, IL-22, IL-24, and IL-26, which are considered as Class 2α-helical cytokines. IL-10 is the most important cytokine in suppressing pro-inflammatory responses in all kinds of autoimmune diseases and limiting excessive immune responses. Due to protein structure homology and shared usage of receptor complexes as well as downstream signaling pathway, other IL-10 family cytokines also show indispensable functions in immune regulation, tissue homeostasis, and host defense. In this review, we focus on immune functions and structures of different cytokines in this family and try to better understand how their molecular mechanisms connect to their biological functions. The molecular details regarding their actions also provide useful information in developing candidate immune therapy reagents for a variety of diseases.


Assuntos
Interleucina-10 , Doenças Autoimunes/imunologia , Humanos , Imunoterapia , Interleucina-10/química , Interleucina-10/imunologia , Transdução de Sinais/imunologia , Relação Estrutura-Atividade
4.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(3): 291-297, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31631592

RESUMO

Objective: To explore the biological characteristics of the esterase LipR encoded by Mycobacterium tuberculosis (MTB) Rv3084 and its immunomodulatory function in vivo. Methods: The LipR gene was amplified from MTB H37Rv strain to construct recombinant expression plasmid. After sequencing, the recombinant plasmid was transformed into E. coli for expression and purification of LipR protein. The expressed protein was confirmed with Western blot assay. The hydrolyzing activity of LipR was detected and the factors affecting LipR enzyme activity were analyzed. Mice were intramuscularly injected with 0.1 mL (containing plasmid DNA 100 µg) recombinant eukaryotic plasmid three times (day 1, 8, and 15); seven days after the last injection, the mice were executed, and the lung and spleen were taken for cytokine detection. Results: The recombinant expression plasmid was successfully constructed and it was found that LipR protein was mainly expressed in the form of inclusion bodies in E. coli with the relative molecular mass of about 33×10 3. LipR was demonstrated as an alkaline eurythermic esterase, due to the preference of hydrolyzing short carbon chain esters with optimal hydrolyzing activity on pNP-acetate (pNPA, C2) and the capability in tolerance of high pH and temperature; in the presence of different detergents or metal ions, the activity of LipR hydrolyzing pNP-butyrate (pNPB, C4) was inhibited to some extent. In the mouse model, it was found that LipR could inhibit the secretion of interferon-γ (IFN- γ) and interleukin-2 (IL-2), but to stimulate the secretion of IL-10. Conclusion: The esterase LipR may be one of the esterases help M. tuberculosis withstand harsh environment inside the host in collaboration, and simultaneously act as an immune modulator to inhibit the secretion of pro-inflammatory cytokines and consequently impact the killing effect of host immune system against M. tuberculosis.


Assuntos
Proteínas de Bactérias/metabolismo , Esterases/metabolismo , Interferon gama/imunologia , Interleucina-10/imunologia , Interleucina-2/imunologia , Mycobacterium tuberculosis/enzimologia , Animais , Camundongos
5.
Medicine (Baltimore) ; 98(40): e17113, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577700

RESUMO

BACKGROUND: Periodontitis is a common disease with an unclear pathological mechanism. No precise consensus has been reached to evaluate the association between the IL-10 rs1800872 (- 592, -590, -597 C>A) polymorphism and periodontal disease. Thus, we performed this meta-analysis to collect more evidence-based information. METHODS: Four online databases, PubMed, Embase, Web of Science, and China Biology Medicine disc (CBM), were searched in August 2018. An odds ratio (OR) with a 95% confidence interval (CI) was applied to evaluate the association of the rs1800872 with periodontitis susceptibility. RESULTS: Twenty three case-control studies with 2714 patients and 2373 healthy controls were evaluated. The overall analyses verified that the IL-10 rs1800872 polymorphism was significantly associated with an increased risk of periodontitis in the allelic model, homozygote model, dominant model, and recessive model (A vs C: OR = 1.28, 95%CI = 1.11-1.49, P = .00, I = 56.87%; AA vs CC: OR = 2.06, 95%CI = 1.32-3.23, P = .00, I = 73.3%; AA + AC vs CC: OR = 1.42, 95%CI = 1.03-1.96, P = .03, I = 76.2%; AA vs AC + CC: OR = 1.78, 95%CI = 1.26-2.56, P = .00, I = 76.7%). Moreover, the subgroup analysis based on ethnicity, periodontitis type, and smoking status showed significant differences. CONCLUSIONS: The results of our meta-analysis demonstrate that rs1800872 is associated with periodontitis susceptibility in Caucasians and Asians. Moreover, A allele, AA genotype, CC genotype may be closely associated with chronic periodontitis (CP), while A allele, AA genotype may be closely associated with aggressive periodontitis (AgP).


Assuntos
Interleucina-10/genética , Periodontite/etnologia , Periodontite/genética , Periodontite Agressiva/etnologia , Periodontite Agressiva/genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China , Periodontite Crônica/etnologia , Periodontite Crônica/genética , Grupo com Ancestrais do Continente Europeu/genética , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Fumar/etnologia
6.
Nihon Yakurigaku Zasshi ; 154(3): 108-113, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31527359

RESUMO

Similar to calcium (Ca2+) and chloride (Cl-) ion channels/transporters, potassium (K+) channels have been recognized as a crucial cancer treatment target. Recent studies have provided convincing evidences of positive correlation between elevated expression levels of Ca2+-activated K+ (KCa) channels and cancer proliferation, metastasis, and poor patient prognosis. In cancer cells, KCa1.1 and KCa3.1 KCa channels are co-localized with Ca2+-permeable Orai/TRP channels to provide a positive-feedback loop for Ca2+ entry. They are responsible for the promotion of cell growth and metastasis in the different types of cancer, and are therefore potential therapeutic targets and biomarkers for cancer. We determined the epigenetic and post-transcriptional dysregulation of KCa3.1 by class I histone deacetylase inhibitors in breast and prostate cancer cells. We further determined the transcriptional repression and protein degradation of KCa1.1 by vitamin D receptor agonists and androgen receptor antagonists, which are expected as potential therapeutic drugs for triple-negative breast cancer. The anti-inflammatory cytokine, interleukin-10 (IL-10) is an immunosuppressive factor involved in tumorigenesis, and plays a crucial role in escape from tumor immune surveillance. We determined KCa3.1 activators are a possible therapeutic option to suppress the tumor-promoting activities of IL-10. These results may provide new insights into cancer treatment focused on Ca2+-activated K+ channels.


Assuntos
Neoplasias da Mama/patologia , Inibidores de Histona Desacetilases/farmacologia , Canais de Potássio Cálcio-Ativados/metabolismo , Neoplasias da Próstata/patologia , Antagonistas de Receptores de Andrógenos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Epigênese Genética , Feminino , Humanos , Vigilância Imunológica , Interleucina-10/metabolismo , Masculino , Proteólise , Processamento Pós-Transcricional do RNA , Receptores de Calcitriol/agonistas
7.
Isr Med Assoc J ; 21(7): 444-448, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31507118

RESUMO

BACKGROUND: Although cross-reactions between Epstein-Barr virus (EBV) and human systemic lupus erythematosus (SLE) autoantigens occur, a complete analysis of the potential EBV peptide cross-reactome has not been performed. OBJECTIVES: To analyze the whole EBV proteome searching for peptides common to SLE-related proteins and endowed with an immunological potential. METHODS: Fifty-one SLE-related proteins were analyzed for hexapeptide sharing with EBV proteome using publicly available databases. RESULTS: An extremely high number of hexapeptides are shared between 34 human SLE autoantigens and EBV proteins. The peptide sharing mostly occurs with complement components C4 and Interleukin-10 (IL-10). CONCLUSIONS: This study thoroughly describes the EBV vs. SLE autoantigens peptide overlap and powerfully supports cross-reactivity as a major mechanism in EBV-associated SLE etiopathogenesis.


Assuntos
Autoantígenos/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Peptídeos/imunologia , Proteoma , Complemento C4/imunologia , Reações Cruzadas/imunologia , Bases de Dados Factuais , Herpesvirus Humano 4/imunologia , Humanos , Interleucina-10/imunologia
8.
Braz Oral Res ; 33: e040, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31508724

RESUMO

The study characterizes dental implant surfaces treated with phosphoric acid to assess the effects of acid treatment on blood cells and correlate them with cytokine levels. The implant surfaces examined were divided into untreated metal surface (US; n = 50), metal surface treated with phosphoric acid (ATS; n = 50) and cement surface (CS; n = 50) groups. The samples were characterized by scanning electron microscopy (SEM) and rheometry. The implants were incubated with human blood mononuclear cells for 24 h, with surface rinsing in the ATS treatment. Cell viability was determined by colorimetric methods and cytokines in the culture supernatant were quantified using flow cytometry. In the ATS group, the surface porosity and contact surface were increased and plaques were observed on the surface. The blood flow and viscosity curves were similar among the treatments, and the high cell viability rates indicate the biocompatibility of the materials used. An increase in the levels of IL-2, IL-4, IL-6, IL-10 and TNF-α was observed in the ATS and CS groups. There were positive correlations between IL-10 and IL-2 levels and between IL-10 and IL-4 levels in the culture supernatant of the ATS group. The results suggest that implant surface treatment with phosphoric acid activates the production of inflammatory cytokines. The increased cytokine levels can modulate the immune response, thereby improving biofunctional processes and promoting the success of dental implants.


Assuntos
Citocinas/análise , Implantes Dentários , Materiais Dentários/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Ácidos Fosfóricos/farmacologia , Anti-Inflamatórios , Sobrevivência Celular , Citocinas/metabolismo , Cimentos Dentários , Humanos , Interleucina-10/análise , Interleucina-10/metabolismo , Microscopia Eletrônica de Varredura , Reologia , Propriedades de Superfície
9.
Life Sci ; 235: 116838, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31493482

RESUMO

AIMS: This work aimed to evaluate the regulatory function of IL-10-producing B cells in viral myocarditis (VMC). MAIN METHODS: We adoptively transferred purified IL-10-producing B cells to VMC mice via the tail vein. We observed the inflammatory responses and cardiac lesions by histological analysis, examined the proportions of spleen Th1 and T17 cells by flow cytometry and expression levels of related transcription factors (T-bet and RORγt) by reverse transcription polymerase chain reaction (RT-PCR), and calculated the cardiac pathological scores and the mean survival times. KEY FINDINGS: IL-10-producing B cells were found to be T cell-dependent in the pathogenesis of VMC. They mainly downregulated T-bet and RORγt mRNA levels to decrease the proportions of Th1 and Th17 cells, thereby restraining the inflammation and damage in the myocardium in B cell-deficient VMC mice. Adoptive transfer of IL-10-producing B cells before VMC induction also normalized the inflammatory responses and prolonged the survival time in wild-type (WT) VMC mice. While the transfer of IL-10-producing B cells on day 3 of VMC alleviated the severity of disease, it did not extend the mean survival time of VMC mice. By contrast, IL-10-producing B cells showed no effect on day 7 of VMC. In conclusion, IL-10-producing B cells downregulate the proportion of Th1 and Th17 cells to alleviate inflammatory damage in the myocardium during VMC before the induction or the early phase of disease. SIGNIFICANCE: These findings suggest that IL-10-producing B cells may be a new therapeutic target for modulating the immune response in VMC.


Assuntos
Linfócitos B/metabolismo , Enterovirus Humano B/imunologia , Inflamação/fisiopatologia , Interleucina-10/fisiologia , Miocardite/fisiopatologia , Células Th1/imunologia , Células Th17/imunologia , Transferência Adotiva , Animais , Infecções por Coxsackievirus/imunologia , Infecções por Coxsackievirus/virologia , Regulação para Baixo , Interleucina-10/biossíntese , Masculino , Camundongos , Miocardite/metabolismo , Miocardite/patologia , Miocardite/virologia , Miocárdio/patologia , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/biossíntese , Taxa de Sobrevida , Proteínas com Domínio T/biossíntese
10.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 54(8): 553-560, 2019 Aug 09.
Artigo em Chinês | MEDLINE | ID: mdl-31378035

RESUMO

Objective: To study the immune regulation function of high expressing interleukin-10 (IL-10) in B cells on CD4(+)T-cells in periodontitis mouse model. Methods: Twenty-four 7-weeks-old female C57BL/6 mice were randomly and equally assigned into 4 groups: the healthy control group (HC group, n=6), the ligation combined Porphyromonasgingivalis (Pg) infection group (P group, n=6), the ligation combined Pg infection with non-stimulated B cell transfer group (P+NSB group, n=6) and the ligation combined Pg infection with stimulated B cell transfer group (P+SB group, n=6). Ligation combined Pg infection of the maxillary second molar was used to induce periodontitis of mice. The exogenous non-stimulated B cells or stimulated B cells were injected into the palate gingivalat the 5th day after ligation, and all mice were sacrificed at the 14th day. HE stain was used to detect the histological of periodontal tissues, toluidine blue stain was used to analysis the alveolar bone loss, immunofluorescence stain was used to detect the expression of CD4(+)T-cell and IL-10, immunohistochemical was used to detect the expression of receptor activator of NF-κB ligand (RANKL) and IL-1ß. Results: Results of HE staining showed that more hyperplasia of gingival epithelium and the alveolar bone resorption in P group, P+NSB group and P+SB group compared with HC group. Results of toluidine blue staining showed that the alveolar bone losses in P group [(0.668±0.041) mm(2)], P+NSB group [(0.750±0.039) mm(2)] and P+SB group [(0.517±0.038) mm(2)] were significantly increased compared with that in HC group [(0.336±0.029) mm(2)](F=146.051, P<0.01), and the alveolar bone resorption was significantly increased in P+NSB group compared with that in P group (F=146.051, P<0.01). However, compared with P+NSB group and P group, the alveolar bone loss in P+SB groupwas significantly decreased (F=146.051, P<0.01). Results of immunofluorescence staining showed that CD4(+)T-cells expressed in P group [(287.5±37.9) cell/mm(2)], P+NSB group [(314.6±53.3) cell/mm(2)] and P+SB group [(185.4±42.9) cell/mm(2)] were higher than that in HC group [(12.5±13.7) cell/mm(2))(F=71.284, P<0.01). Compared with P group and P+NSB group, CD4(+)T-cells expression in group P+SB was decreased (F=71.284, P<0.01). IL-10 levels were increased in P group [(111.7±20.4) cell/mm(2)], P+NSB group [(126.7±15.1) cell/mm(2)] and P+SB group [(191.0±22.6) cell/mm(2)] compared with that in HC group [(22.7±4.3) cell/mm(2)] (F=98.516, P<0.01), and the IL-10 expressed in P+SB group was significantly higher than those in P+NSB group and P group. Results of immunohistochemical tests showed that RANKL expressions in gingival tissues among P group [(674.0±71.5) cell/mm(2)], P+NSB group [(831.0±97.5) cell/mm(2)] and P+SB group [(420.1±40.8) cell/mm(2)] were significantly higher than that in HC group [(69.3±29.1) cell/mm(2)] (F=154.886, P<0.01). However, it dramatically decreased in P+SB group compared with those in P group and P+NSB group.The IL-1ßexpression in P group [(447.8±40.8) cell/mm(2)], P+NSB group [(512.5±38.2) cell/mm(2)] and P+SB group [(281.6±32.4) cell/mm(2)] were significantly higher than that in HC group [(50.8±20.9) cell/mm(2)], and it also higher in P+NSB group compared with in P group. However, it decreased in P+SB group compared with those in P group and P+NSB group (F=221.185, P<0.01). Conclusions: High expression IL-10 in B cell smight inhibit alveolar bone loss, RANKL and IL-1ß expressions and CD4(+)T-cell infiltration through IL-10.


Assuntos
Perda do Osso Alveolar , Linfócitos B , Periodontite , Linfócitos T , Animais , Antígenos CD4 , Feminino , Interleucina-10 , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória
11.
Sheng Li Xue Bao ; 71(4): 575-580, 2019 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-31440754

RESUMO

The aim of the present study was to investigate the effect of salidroside (Sal) on inflammatory activation induced by lipopolysaccharide (LPS) in the co-culture of rat alveolar macrophages (AM) NR 8383 and type II alveolar epithelial cells (AEC II) RLE-6TN. CCK-8 colorimetric method was used to detect cell proliferation percentage. The enzyme-linked immunosorbent assay (ELISA) was used to determine the content of tumor necrosis factor alpha (TNF-α), macrophage inflammatory protein-2 (MIP-2) and interleukin-10 (IL-10) in the supernatant. Western blot was used to examine the expression levels of phosphorylated AKT (p-AKT) and total AKT protein. The results showed that pretreatment of RLE-6TN cells or co-culture of RLE-6TN and NR 8383 cells with 32 and 128 µg/mL Sal for 1 h, followed by continuous culture for 24 h, significantly increased the cell proliferation (P < 0.05). Compared with control group, 32 and 128 µg/mL Sal pretreatment significantly increased the ratio of p-AKT/AKT in RLE-6TN cells (P < 0.05). Pretreatment of 32 µg/mL Sal not only inhibited the secretion of TNF-α and MIP-2 by NR 8383 cells induced by LPS (P < 0.05), but also enhanced the inhibitory effect of RLE-6TN and NR 8383 cells co-culture on the secretion of TNF-α and MIP-2 by NR 8383 cells induced by LPS (P < 0.05). In addition, 32 µg/mL Sal pretreatment promoted LPS-induced IL-10 secretion by NR 8383 cells (P < 0.05), and enhanced the promoting effect of co-culture of RLE-6TN and NR 8383 cells on the IL-10 secretion by LPS-induced NR 8383 cells (P < 0.05). In conclusion, Sal may directly inhibit LPS-induced inflammatory activation of AM (NR 8383), promote the proliferation of AEC II (RLE-6TN) through PI3K/AKT signaling pathway, and enhance the regulatory effect of AEC II on LPS-induced inflammatory activation of AM.


Assuntos
Células Epiteliais Alveolares/efeitos dos fármacos , Glucosídeos/farmacologia , Macrófagos Alveolares/efeitos dos fármacos , Fenóis/farmacologia , Transdução de Sinais , Células Epiteliais Alveolares/metabolismo , Animais , Linhagem Celular , Quimiocina CXCL2/metabolismo , Técnicas de Cocultura , Interleucina-10/metabolismo , Lipopolissacarídeos , Macrófagos Alveolares/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Fator de Necrose Tumoral alfa/metabolismo
12.
Zhen Ci Yan Jiu ; 44(6): 405-11, 2019 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-31368262

RESUMO

OBJECTIVE: To observe the influence of scalp acupuncture on cerebral infarct size and expression of IL-10, IL-6, and IL-1ß in the para-hippocampal gyrus in acute ischemic cerebrovascular disease(AICD) rats, so as to investigate its mechanisms underlying improvement of AICD. METHODS: Forty-eight male SD rats were randomly allocated to normal control (control), AICD model, medication, and scalp acupuncture groups (n=12 per group). The AICD model was established by occlusion of the middle cerebral artery (MCAO). Rats of the medication group received intraperitoneal injection of Ammonium 1-Pyrrolidinedithiocarbamate (APDC, 100 mg•kg-1•d-1), once daily for 7 days. Scalp acupuncture stimulation was applied to bilateral "Dingnieqianxiexian" (MS6) once daily for 7 days. Before and after intervention, the neurologic deficit score (NDS) and the neurological score (NS) were evaluated according to Longa's and Schäbitz's methods, respectively. At the end of the intervention, the para-hippocampal gyrus and whole brain were collected respectively. The expression levels of IL-10, IL-6 and IL-1ß in the para-hippocampal gyrus tissue were detected by immunohistochemistry, and the cerebral infarct volume of the brain was detected by triphenyltetrazollium chloride (TTC) staining after sectioning. RESULTS: Following modeling, the NDS, NS and the expression of IL-10, IL-6 and IL-1ß in para-hippocampal gyrus were significantly increased in the model group compared with the control group (P<0.01). After the intervention, the NDS, NS and infarct volume, and the expression levels of IL-6 and IL-1ß in the para-hippocampal gyrus were significantly decreased in both medication and scalp acupuncture groups compared with the model group (P<0.05), and the expression of IL-10 was further obviously up-regulated in the scalp acupuncture group (P<0.05) rather than in the medication group (P>0.05). The effect of scalp acupuncture was obviously superior to that of medication in up-regulating IL-10 expression level (P<0.05). No significant differences were found between the medication and scalp acupuncture groups in the levels of NDS, NS, infarct volume, IL-6 and IL-1ß proteins (P>0.05). CONCLUSION: Scalp acupuncture can improve neurological function and reduce infarct volume in AICD rats, which may be associated with its function in up-regulating the expression of IL-10 and in inhibiting the expression of IL-6 and IL-1ß to reduce inflammation reaction.


Assuntos
Terapia por Acupuntura , Isquemia Encefálica , Animais , Interleucina-10 , Interleucina-1beta , Interleucina-6 , Masculino , Giro Para-Hipocampal , Ratos , Ratos Sprague-Dawley , Couro Cabeludo
13.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(8): 789-795, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31416504

RESUMO

OBJECTIVE: To study the association of interleukin-10 (IL-10) -1082A/G, -819C/T, and -592C/A polymorphisms with IL-10 level and the severity of enterovirus 71 (EV71) infection in children. METHODS: A total of 137 children with hand-foot-mouth disease due to EV71 infection were enrolled as EV71 infection group, which was further divided into mild group with 91 children and severe group with 46 children, and 122 healthy children who underwent physical examination were enrolled as healthy control group. Related clinical data were collected. ELISA was used to measure the serum level of IL-10, and polymerase chain reaction-restriction fragment length polymorphism was used to analyze IL-10 -1082A/G, -819C/T and -592C/A polymorphisms. RESULTS: Compared with the healthy control group, the children with EV71 infection had significantly higher frequency of -1082 AA genotype and A allele (P<0.05). Among the children with EV71 infection, the severe group had significantly higher frequency of -1082 AA genotype and A allele than the mild group (P<0.05), while there was no significant difference in the distribution of IL-10 -819C/T and IL-10 -592C/A polymorphisms between the two groups (P>0.05). The severe group had a significantly higher serum level of IL-10 than the mild group and the healthy control group. IL-10 -1082 AA genotype, -819 TT genotype, and -592 AA genotype were associated with the low expression of IL-10 (P<0.05). As for haplotype, the EV71 infection group had a significantly lower frequency of GCC haplotype than the healthy control group (P<0.05). In the severe group, the children with ATA haplotype had a significantly lower IL-10 level than those with other haplotypes, and the children with GCC haplotype had a significantly higher IL-10 level than those with other haplotypes (P<0.05). There was no significant difference in IL-10 level between children with different haplotypes in the mild group and the healthy control group (P>0.05). CONCLUSIONS: IL-10 gene polymorphisms are associated with IL-10 expression and the severity of EV71 infection in children.


Assuntos
Enterovirus Humano A , Infecções por Enterovirus , Interleucina-10/genética , Criança , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Polimorfismo de Nucleotídeo Único
14.
Medicine (Baltimore) ; 98(33): e16848, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415412

RESUMO

BACKGROUND: The aim of this study was to investigate the expression of tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) in expressed prostatic secretions (EPSs) of patients with chronic prostatitis (CP) and the expression of prostatic exosomal protein (PSEP) in urine, and to evaluate its correlation with the condition. METHODS: Urine samples from 310 patients with CP (101 National Institutes of Health [NIH] II, 112 NIH IIIa, and 97 NIH IIIb, classified according to the US National Institutes of Health) and 110 control group subjects were collected. The samples were tested for PSEP by enzyme-linked immunosorbent assay (ELISA). At the same time, EPSs in 60 patients from 310 patients with CP and 20 control group subjects were collected. The levels of IL-10 and TNF-α in the collected samples that EPS were determined by double antibody sandwich ELISA. SPSS 23.0 statistical software was used for statistical analysis of the measured data. RESULTS: The level of PSEP in patients with CP was significantly higher than that in the control group (P < .001). The levels of TNF-α and IL-10 in the EPS of patients with NIH II and NIH IIIa CP were higher than those of the patients with NIH IIIb and the control group (P < .001). There was a positive correlation between PSEP and IL-10 and TNF-α, while TNF-α and IL-10 were also positively correlated. CONCLUSION: PSEP, TNF-α, and IL-10 may serve as a basis for the classification diagnosis of CP. Their combination can provide more accurate diagnostic information for clinical CP typing.


Assuntos
Exossomos/metabolismo , Interleucina-10/urina , Próstata/metabolismo , Prostatite/urina , Fator de Necrose Tumoral alfa/urina , Adulto , Biomarcadores/urina , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Humanos , Masculino , Pessoa de Meia-Idade , Prostatite/diagnóstico , Curva ROC , Adulto Jovem
15.
Adv Clin Exp Med ; 28(9): 1243-1248, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31430072

RESUMO

BACKGROUND: FoxP3 is a marker of human T regulatory cells (Tregs), which are supposed to play an important role in the pathophysiology of atherosclerosis. Interleukin 10 (IL-10) is a cytokine with pleiotropic, immunoregulatory properties, produced mostly by Tregs and B regulatory cells. Due to their anti-inflammatory action, both Tregs and IL-10 are believed to inhibit plaque development and decrease atherosclerosis progression. The effect of hypolipidemic drugs - statins or ezetimibe - on FoxP3-positive Tregs and anti-inflammatory cytokines, such as IL-10, is still unclear. OBJECTIVES: The objective of the study was to investigate the effects of 3 different therapies of equivalent hypolipidemic activity: atorvastatin, rosuvastatin, and combination therapy of atorvastatin and ezetimibe on FoxP3-Tregs transcription factor and IL-10 mRNA expression in peripheral blood mononuclear cells (PBMCs) from patients with stable coronary artery disease (CAD). MATERIAL AND METHODS: Sixty-five patients with diagnosed CAD participated in the study. They were randomly assigned to 3 therapeutic groups: atorvastatin at a dose of 40 mg/day (A40 group); rosuvastatin 20 mg/day (R20 group); and atorvastatin 10 mg/day combined with ezetimibe 10 mg/day (A10+E10 group). After 1 month and 6 months of therapy, the mRNA expression for FoxP3 and IL-10 in PBMCs was evaluated using real-time polymerase chain reaction (RT-PCR) and lipid parameters. RESULTS: An improvement in lipid parameters was observed in each of the groups studied; however, hypolipidemic treatment did not induce any change in FoxP3 and IL-10 mRNA expression. After 6 months, an increase in FoxP3 mRNA expression was noted in A40 group as compared to R20 group. CONCLUSIONS: None of the therapies of equal hypolipidemic efficacy affected FoxP3 and IL-10 mRNA expression in patients with stable CAD.


Assuntos
Anticolesterolemiantes , Doença da Artéria Coronariana , Inibidores de Hidroximetilglutaril-CoA Redutases , Anticolesterolemiantes/uso terapêutico , Atorvastatina/uso terapêutico , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/metabolismo , Ezetimiba/uso terapêutico , Fatores de Transcrição Forkhead/metabolismo , Regulação da Expressão Gênica , Humanos , Interleucina-10/metabolismo , Leucócitos Mononucleares , RNA Mensageiro
16.
Chem Biol Interact ; 311: 108758, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31348919

RESUMO

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder in children. It is diagnosed by two main behavioral phenotypes i.e. social-communication impairments and repetitive behavior. ASD is complex disorder with unsolved etiology due to multiple genes involvement, epigenetic mechanism and environmental factors. The clinical and preclinical studies have been indicating the association of propionic acid with autism spectrum disorder. Numerous studies suggest the potential therapeutic effects of peroxisome proliferator-activated receptor-gamma (PPAR-γ) in different brain disorders. This research evaluates the utility of selective agonist of PPAR-γ, pioglitazone in postnatal propionic acid induced ASD related symptomatology in male Wistar rats. PPA (250 mg/kg, p.o.) was administered to male offspring for three consecutive days from postnatal 21st day to 23rd day. PPA induced social impairment, repetitive behavior, hyperlocomotion, anxiety and low exploratory activity in rats. Also, postnatal propionic acid-treated rats showed higher levels of oxidative stress (increased in thiobarbituric acid reactive species and decreased in reduced glutathione) as well as inflammation (increased in interleukin-6, tumor necrosis factor-alpha and decreased in interleukin-10) in the cerebellum, brainstem and prefrontal cortex. The rats were treated daily with pioglitazone (10 mg/kg and 20 mg/kg, p.o.) from postnatal 24th day to end of the study. Treatment with pioglitazone, significantly attenuated the postnatal propionic acid-induced social impairment, repetitive behavior, hyperactivity, anxiety and low exploratory activity. Furthermore, pioglitazone also reduced the postnatal propionic acid-induced oxidative stress and neuroinflammation in aforementioned brain regions. Hence, pioglitazone improved the propionic acid-induced neurobehavioral and biochemical impairments in rats.


Assuntos
Transtorno do Espectro Autista/patologia , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/agonistas , Pioglitazona/farmacologia , Animais , Ansiedade/prevenção & controle , Transtorno do Espectro Autista/induzido quimicamente , Transtorno do Espectro Autista/metabolismo , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Glutationa/metabolismo , Inflamação/prevenção & controle , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Locomoção/efeitos dos fármacos , Masculino , PPAR gama/metabolismo , Fenótipo , Pioglitazona/uso terapêutico , Propionatos/toxicidade , Ratos , Ratos Wistar
17.
Artigo em Chinês | MEDLINE | ID: mdl-31256526

RESUMO

Objective: To study the changes of monocyte cytokines in peripheral blood of n-hexane neuropathy patients induced by P(0) protein, and to explore the role of autoimmunity in n-hexane neuropathy patients. Methods: In May 2018, 5 patients with peripheral neuropathy diagnosed as n-hexane poisoning were selected as case group in Shenzhen Prevention and Treatment Center for Occupational Disease in 2017. 6 workers exposure to n-hexane and 6 workers without n-hexane exposure were selected as contact group and control group. Peripheral blood mononuclear cells(PBMC) were isolated from venous blood. Results: The number of spots produced by INF-γ and IL-10 increased after stimulation with P(0) protein in case group, and the positive rate was significantly higher than control group and the contact group. Conclusion: Autoimmunity induced by P(0) protein may be involved in the occurrence of myelin sheath damage in n-hexane neuropathy patients.


Assuntos
Doenças do Sistema Nervoso Periférico , Hexanos , Humanos , Interleucina-10 , Leucócitos Mononucleares , Doenças do Sistema Nervoso Periférico/induzido quimicamente
18.
BMC Complement Altern Med ; 19(1): 163, 2019 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-31277636

RESUMO

BACKGROUND: Therapeutic vaccines against cervical cancer remain ineffective. Previously, we demonstrated that blocking the signalling of a cytokine, interleukin 10, at the time of immunisation elicited significantly higher numbers of antigen specific T cells and inhibited tumour growth in mice. RESULTS: In the current paper, we demonstrate, in a HPV16 E6/E7 transformed TC-1 tumour mouse model, that despite increased antigen specific T cell numbers, blocking IL-10 signalling at the time of immunisation does not increase the survival time of the TC-1 tumour bearing mice compared to mice receiving the same immunisation with no IL-10 signalling blockade. Moreover, the function of tumour infiltrating T cells isolated 3 weeks post TC-1 transplantation is more suppressed than those isolated 2 weeks after tumour inoculation. We demonstrate that synthesized caerin peptides, derived from amphibian skin secretions, 1) were able to inhibit TC-1 tumour growth both in vitro and in vivo; 2) are environmentally stable; and 3) promote the secretion of pro-inflammatory interlukine-6 by TC-1 cells. Notably caerin peptides were able to increase the survival time of TC-1 tumour bearing mice after therapeutic vaccination with a HPV16E7 peptide-based vaccine containing IL-10 inhibitor, via recruiting increased levels of T cells to the tumour site. CONCLUSION: Caerin peptides increase the efficacy of a therapeutic vaccine by recruiting more T cells to the tumour site.


Assuntos
Proteínas de Anfíbios/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Vacinas Anticâncer/uso terapêutico , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Proteínas de Anfíbios/uso terapêutico , Animais , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Vacinas Anticâncer/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Células HeLa , Humanos , Interleucina-10/antagonistas & inibidores , Interleucina-6/metabolismo , Linfócitos do Interstício Tumoral/metabolismo , Camundongos Endogâmicos C57BL , Transplante de Neoplasias , Neoplasias Experimentais/tratamento farmacológico , Linfócitos T/metabolismo
19.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(7): 708-712, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31315773

RESUMO

OBJECTIVE: To construct the recombinant adenoviral vector carrying the rat interleukin-10 (rIL-10) gene, and to investigate whether it is stably expressed in bone marrow mesenchymal stem cells. METHODS: The rIL-10 gene was amplified by PCR from template rIL-10 cDNA, and the recovered 656 bp rIL-10 DNA fragment was cloned into pcDNA3.1 to construct pcDNA3.1-IL-10. Then HEK293 cells were transfected with pcDNA3.1-IL-10 and adenoviral vector for homologous recombination, and sequencing and PCR were used to evaluate whether recombination was successful. HEK293 cells were lysed by repeated freeze-thaw cycles, and bone marrow mesenchymal stem cells were infected with the virus solution containing the rIL-10 gene. Western blot was used to measure the expression of rIL-10 in bone marrow mesenchymal stem cells. RESULTS: Sequencing and PCR verified that the rIL-10 adenoviral vector was successfully constructed, with a virus titer of 4×109 PFU/mL. The expression of IL-10 was detected after bone marrow mesenchymal stem cells were infected by the virus solution containing the rIL-10 gene. CONCLUSIONS: The constructed rIL-10 recombinant adenovirus can mediate the stable expression of rIL-10 gene in bone marrow mesenchymal stem cells, which provides a basis for gene transplantation therapy of inflammatory bowel disease.


Assuntos
Células-Tronco Mesenquimais , Adenoviridae , Animais , Células da Medula Óssea , Vetores Genéticos , Células HEK293 , Humanos , Interleucina-10 , Ratos , Transfecção
20.
Braz Oral Res ; 33: e033, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31269113

RESUMO

The aim of this study was to evaluate the effect of periodontal treatment on the salivary cytokine levels and clinical parameters of individuals with cerebral palsy (CP) with gingivitis. A non-randomized, clinical trial was conducted in individuals diagnosed with spastic CP. Thirty-eight individuals were enrolled in the study and were categorized according to gingival index scores between 0-1 or 2-3, assigned to groups G2 or G1, respectively. Periodontal treatment comprised oral hygiene instructions, conventional mechanical treatment and 0.12% chlorhexidine applied as an adjunct. Clinical parameters and saliva samples were collected at baseline and at the 15-day follow-up visit. Bleeding on probing and periodontal screening and recording were determined. Non-stimulated saliva samples were obtained, and the salivary flow rate, the osmolality and the levels of cytokines IL-1ß, IL-6, IL-8, IL-10, TNF-α and IL-12p70 were evaluated by a cytometric bead array. The Wilcoxon test, the Mann-Whitney test, Spearman correlation analysis, Poisson regression analysis and an adjusted analysis were performed (α = 0.05). The groups differed significantly in periodontal clinical parameters at baseline and at follow-up. Salivary flow rate and osmolality were similar in both groups at both timepoints. However, TNF-α and IL-1ß levels were higher in G1 than in G2 at baseline. Mechanical treatment resulted in improved clinical parameters for both groups. Furthermore, mechanical treatment resulted in a significant reduction in salivary IL-1ß and IL-8 levels for both groups after treatment. Periodontal treatment performed in individuals with CP and gingivitis reduces the levels of TNF-α, IL-1ß, IL-6 and IL-8.


Assuntos
Biomarcadores/análise , Paralisia Cerebral/complicações , Gengivite/complicações , Gengivite/reabilitação , Periodontite/terapia , Saliva/química , Adolescente , Criança , Citocinas/análise , Profilaxia Dentária/métodos , Feminino , Gengivite/microbiologia , Humanos , Interleucina-10 , Interleucina-1beta/análise , Interleucina-6/análise , Masculino , Concentração Osmolar , Índice Periodontal , Distribuição de Poisson , Saliva/imunologia , Saliva/microbiologia , Fator de Necrose Tumoral alfa/análise
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