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1.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(4): 351-354, 2019 Jul 28.
Artigo em Chinês | MEDLINE | ID: mdl-31701721

RESUMO

OBJECTIVE: To study the preventive and therapeutic effects of safflower water extract on systemic scleroderma (SSc) in mice and its mechanism. METHODS: Sixty BALB/C mice were randomly divided into the control group, model group, prednisone group and safflower low, middle, high dose groups, 10 mice in each group.The control group was injected with normal saline, and the other five groups were subcutaneously injected with bleomycin hydrochloride with 100 µl at the concentration of 200 µg /ml on the back, once a day for 28 days to establish the SSc models.At the same time, the control group and model group were treated with normal saline (10 ml/kg), the prednisone group was treated with prednisone 4.5 mg/kg (10 ml/kg), and the low, middle, and high dose safflower groups were treated with safflower at the doses of 1.5, 3, 6 g/kg (10 ml/kg), and all groups were treated for 28 days.After 28 days, all mice were decapitated. The blood samples and back skin of the BLM injection part were collected.After that, all the tissue slices were taken to measure the dermal thickness, and the content of hydroxyproline (HYP) in the skin tissues was detected by hydrolysis method.The contents of tissue growth factor (CTGF) and transforming growth factor-ß (TGF-ß ) in the skin tissues and the levels of interleukin-6 (IL-6) and interleukin-17 (IL-17) in serum were determined by ELISA. RESULTS: Compared with the control group, the dermal thickness of the model group was increased(P<0.05), the contents of CTGF, TGF-ß and HYP in the skin tissues and the levels of IL-6 and IL-17 in the serum of the model group were increased(P<0.05); compared with the model group, the dermal thickness in the prednisone group and safflower groups was decreased (P<0.05), the levels of CTGF, TGF-ß and HYP in the skin tissues and the serum levels of IL-6 and IL-17 in the prednisone group and safflower groups were decreased (P<0.05). CONCLUSION: Safflower water extract can improve skin condition (or dermal thickness) in SSc mice, and its mechanism may be related to reducing immune inflammatory response.


Assuntos
Carthamus tinctorius/química , Extratos Vegetais/farmacologia , Escleroderma Sistêmico/tratamento farmacológico , Animais , Bleomicina , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Modelos Animais de Doenças , Hidroxiprolina/análise , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Aleatória , Pele/patologia , Fator de Crescimento Transformador beta1/metabolismo
2.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(8): 983-988, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31537224

RESUMO

OBJECTIVE: To explore the immunomodulatory effects of interleukin-17 (IL-17) on acute lung injury (ALI) induced by lipopolysaccharide (LPS). METHODS: Thirty-six SPF-class C57BL/6 mice were divided into normal saline control group (NS group) and LPS-induced ALI model group (LPS group, LPS 5 mg/kg intratracheal drip) according to random number table method, with 18 mice in each group. Six mice were sacrificed at 2, 6 and 24 hours after model reproduction, and peripheral blood, lung and spleen tissues were harvested. After staining with hematoxylin-eosin (HE), the pathological changes of lung tissue were observed under microscope and the infiltration level of lymphocytes, neutrophils and macrophages in the alveolar wall and tracheal wall were detected. Immunohistochemistry was used to detect the protein expression of IL-17 in alveolar wall and tracheal wall, and the correlation between IL-17 expression and lymphocytes, neutrophils and macrophages infiltration in alveolar wall and tracheal wall were analyzed. The level of IL-17 in lung tissue homogenate was determined by enzyme linked immunosorbent assay (ELISA). Flow cytometry was used to detect the proportion of CD4+IL-17+ helper T cells (Th17 cells) in CD4+ T cells in peripheral blood, lung tissue and spleen tissue. RESULTS: (1) Microscopy showed that the lung tissue structure of NS group was basically normal at each time after model reproduction, and there was no obvious inflammatory cell infiltration, while the lung tissue edema and inflammatory reaction were gradually aggravated in the LPS group, and the lung injury score was significantly higher than that in NS group at each time (2 hours: 4.47±1.42 vs. 1.10±0.55, 6 hours: 7.93±2.14 vs. 1.23±0.50, 24 hours: 12.67±2.67 vs. 1.20±0.61, all P < 0.01). (2) Immunohistochemistry showed that the protein expression of IL-17 in alveolar wall and tracheal wall of LPS group increased gradually with time, while that in NS group was negative or weak positive. Quantitative analysis showed that the immunohistochemical staining score of IL-17 protein in alveolar wall and tracheal wall of LPS group were higher than those of NS group (alveolar wall: 2.70±1.40 vs. 0.90±0.37 at 2 hours, 5.10±1.76 vs. 1.17±0.59 at 6 hours, 9.67±1.32 vs. 1.10±0.45 at 24 hours; tracheal wall: 2.87±0.89 vs. 0.90±0.39 at 2 hours, 4.97±1.48 vs. 1.10±0.41 at 6 hours, 8.67±1.54 vs. 1.03±0.29 at 24 hours; all P < 0.05). (3) Correlation analysis showed that the protein expression of IL-17 in alveolar wall and tracheal wall were positively correlated with the degree of lymphocyte, neutrophil and macrophage infiltration (alveolar wall: r value was 0.632, 0.550, 0.466; tracheal wall: r value was 0.695, 0.662, 0.575, respectively; all P < 0.01). (4) IL-17 content (µg/L) in lung tissue homogenate was significantly higher than that in NS group at each time after model reproduction (2 hours: 1.37±0.14 vs. 1.01±0.18, 6 hours: 1.65±0.19 vs. 1.11±0.18, 24 hours: 1.92±0.36 vs. 1.17±0.24, all P < 0.01). (5) The proportion of Th17 cells in the peripheral blood, lung tissue and spleen tissue of the LPS group were higher than those of the NS group at each time after model reproduction [peripheral blood: (2.62±0.62)% vs. (1.42±0.40)% at 2 hours, (3.74±0.43)% vs. (1.27±0.32)% at 6 hours, (4.44±0.65)% vs. (1.59±0.45)% at 24 hours; lung tissue: (2.32±0.44)% vs. (1.50±0.25)% at 2 hours, (3.66±0.36)% vs. (1.33±0.24)% at 6 hours, (4.60±0.54)% vs. (1.60±0.27)% at 24 hours; spleen tissue: (1.49±0.36)% vs. (0.69±0.21)% at 2 hours, (2.58±0.55)% vs. (0.59±0.18)% at 6 hours, (3.76±0.57)% vs. (0.65±0.26)% at 24 hours; all P < 0.01]. CONCLUSIONS: IL-17 is involved in the inflammatory immune regulation of ALI mice.


Assuntos
Lesão Pulmonar Aguda/metabolismo , Interleucina-17/metabolismo , Animais , Lipopolissacarídeos , Pulmão , Camundongos , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa
3.
Presse Med ; 48(9): 919-930, 2019 Sep.
Artigo em Francês | MEDLINE | ID: mdl-31543394

RESUMO

Giant cell arteritis (GCA) is a large-vessel vasculitis involving the aorta and its main branches, especially supra aortic branches. Although much progress has been made, the pathophysiology remains incompletely understood. An initial trigger, suspected of infectious origin, lead to the maturation and recruitment of dendritic cells (DC). The lack of migration of these DC allows the local recruitment of T-lymphocytes (LT). These LT- CD4+ polarize in Type 1 helper (Th1), Th17 but also Th9. A qualitative and quantitative deficit in regulatory T cells (Treg) is observed under the influence of IL-21 overproduction. In addition, an imbalance in the Th17/Treg balance is favored by IL-6. The secretion of IFN-γ, IL-17, IL-6, IL-33 is responsible for a sustained local inflammatory reaction that is organized around tertiary lymphoid follicles. Locally recruited macrophages secrete reactive forms of oxygen together with VEGF and PDGF. These growth factors, together with neurotrophins and endothelin contribute to increase the proliferation of vascular smooth muscle cells (VSMCs). The imbalance between matrix metalloproteases (MMP)-2, MMP-9 and MMP-14 and tissue inhibitors of metalloproteases (TIMP)-1 and TIMP-2 also contribute to the remodeling process occurring in the vessel wall. Finally, arterial neovascularization contribute to the perpetuation of lymphocyte recruitment. This persistent remodeling is sometimes complicated by ischemic events responsible for the initial severity of the disease.


Assuntos
Arterite de Células Gigantes/fisiopatologia , Remodelação Vascular/fisiologia , Animais , Linfócitos B/fisiologia , Linfócitos T CD4-Positivos/fisiologia , Movimento Celular , Proliferação de Células , Células Dendríticas/fisiologia , Modelos Animais de Doenças , Predisposição Genética para Doença , Arterite de Células Gigantes/tratamento farmacológico , Arterite de Células Gigantes/etiologia , Arterite de Células Gigantes/patologia , Humanos , Interferon gama/metabolismo , Interleucina-17/metabolismo , Interleucina-33/metabolismo , Interleucina-6/fisiologia , Interleucinas/biossíntese , Ativação Linfocitária/fisiologia , Macrófagos/metabolismo , Metaloproteinases da Matriz/metabolismo , Músculo Liso Vascular/patologia , Neovascularização Patológica/fisiopatologia , Linfócitos T Reguladores/fisiologia , Células Th17/fisiologia
4.
APMIS ; 127(12): 789-796, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31512766

RESUMO

The aim was to examine anti-tumor necrosis factor α (anti-TNFα) therapy influence changes on Th17 and Th22 cells in patients with spondyloarthritis (SpA), and its correlation with changes in clinical and magnetic resonance imaging (MRI) activity and chronicity scores. The Th17 and Th22 cells were assessed at baseline, after 12 and 52 weeks of anti-TNFα therapy by flow cytometry (ClinicalTrials.gov NCT4682724). The percentages of both Th17 and Th22 cells were increased by 70% at baseline compared with healthy controls (both p < 0.01). During treatment, these two subsets increased further to be 170% (Th17) and 123% (Th22) above levels in healthy controls (both p < 0.01). The same subsets decrease their expression of IL-23R significantly during the observation period (p < 0.05). High levels of Th17 and Th22 cells at baseline were associated with the degree of chronic changes in the sacroiliac joints on MRI and a good clinical response to anti-TNFα treatment after one year. Plasma levels were not associated with clinical changes. Th17 cells, and Th22 subsets, increased during one year of anti-TNF-α therapy in SpA, regardless of their clinical improvement. This supports that both the Th17 and Th22 subsets could be involved in the progression in SpA.


Assuntos
Anti-Inflamatórios/uso terapêutico , Espondilartrite/tratamento farmacológico , Linfócitos T Auxiliares-Indutores/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Anti-Inflamatórios/farmacologia , Feminino , Citometria de Fluxo , Humanos , Interleucina-17/metabolismo , Interleucinas/metabolismo , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Receptores de Interleucina/metabolismo , Espondilartrite/diagnóstico por imagem , Espondilartrite/imunologia , Espondilartrite/patologia , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Células Th17/metabolismo , Resultado do Tratamento
5.
Biol Res ; 52(1): 49, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492195

RESUMO

BACKGROUND: Psoriasis is a common and intractable skin disease affecting the physical and mental health of patients. The accumulation of ROS is involved in the pathogenesis of psoriasis and antioxidants are believed to be therapeutic. This study aimed to investigate the therapeutic efficacy of astilbin on ROS accumulation in psoriasis. RESULTS: The study showed that 50 µg/ml astilbin could inhibit the growth and reduce the accumulation of ROS in HaCaT cells stimulated by IL-17 and TNF-α. Astilbin could elevate the Nrf2 accumulation in the nuclei, eventually leading to the transcriptional activation of various antioxidant proteins and reducing the expression of VEGF. CONCLUSIONS: Our results collectively suggest that astilbin could induce Nrf2 nucleus translocation, which is contribute to reduce the ROS accumulation and VEGF expression, and inhibit the proliferation of HaCaT cells.


Assuntos
Flavonóis/administração & dosagem , Queratinócitos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Psoríase/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Interleucina-17/metabolismo , Queratinócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fator 2 Relacionado a NF-E2/metabolismo , Psoríase/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
6.
Exp Parasitol ; 206: 107767, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31520603

RESUMO

Schistosoma mansoni eggs can influence immune responses directed at them, and the mechanisms by which this is achieved are being unravelled. Going towards, developing effective tools for the study of how S. mansoni influences naïve T cells, we have developed S. mansoni eggs expressing chicken ovalbumin (OVA), using a lentiviral transduction system. Indeed, such a parasite could be used in conjunction with cells from OT-II transgenic mice as a source of naïve, antigen-specific T cells. The expression of the transgenic protein was confirmed by real-time RT-PCR of OVA-specific mRNA and western blotting using polyclonal antibodies specific for OVA. T cells from OT-II transgenic mice expressing a T cell receptor specific for the OVA323-339 peptide recognised the OVA-transduced S. mansoni eggs. Using flow cytometry on CFSE-labelled OT-II splenocytes, we demonstrated that OVA-transduced eggs elicit higher OT-II proliferative responses than untransduced eggs. The OT-II T cells also produced TNF-α and IFN-γ following exposure to OVA-transduced eggs. In addition, moderate amounts of IL-6 and IL-17A were also detected. In contrast, no IL-10, IL-4 and IL-2 were detected in cultures, whether the cells were stimulated with transduced or untransduced eggs. Thus, the cytokine signatures showed the transfected eggs induced predominantly a Th1 response, with a small amount of IL-6 and IL-17.


Assuntos
Ovalbumina/análise , Receptores de Antígenos de Linfócitos T/imunologia , Schistosoma mansoni/metabolismo , Linfócitos T/imunologia , Animais , Western Blotting , Galinhas , Citocinas/análise , Citocinas/metabolismo , Eletroforese em Gel de Ágar , Feminino , Citometria de Fluxo , Interleucina-17/análise , Interleucina-17/metabolismo , Interleucina-2/análise , Interleucina-2/metabolismo , Interleucina-6/análise , Interleucina-6/metabolismo , Fígado/parasitologia , Linfonodos/citologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Ovalbumina/genética , Ovalbumina/imunologia , Ovalbumina/metabolismo , Óvulo/metabolismo , RNA Mensageiro/análise , RNA Mensageiro/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Antígenos de Linfócitos T/genética , Transcrição Reversa , Schistosoma mansoni/genética , Schistosoma mansoni/crescimento & desenvolvimento , Baço/citologia , Linfócitos T/citologia
7.
Cancer Sci ; 110(10): 3068-3078, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31432577

RESUMO

The programmed cell death 1/programmed cell death 1 ligand 1 pathway was successfully targeted in cancer immunotherapy. Elevated interleukin-17 (IL-17), which is known in autoimmune diseases, has recently been recognized in cancer patients. We investigated the role of IL-17 in the regulation of expression of programmed cell death 1 ligand 1 in ovarian cancer by evaluating changes in the number of IL-17-producing cluster of differentiation 4 helper T cells (Th17) and γδT cells (γδT17) in PBMC of 52 gynecological cancer patients (including 30 ovarian cancer patients) and 18 healthy controls. The occupancy ratio of Th17 and γδT17 was higher in ovarian cancer and endometrial cancer patients than in controls, determined by multi-color flow cytometry (Th17: P < 0.0001 and P = 0.0002, respectively; γδT17: P = 0.0020 and P = 0.0084, respectively). IL-17 mRNA level was elevated in PBMC of ovarian cancer patients (P = 0.0029), as measured by RT-PCR. The neutrophil-to-lymphocyte ratio, which is a prognostic biomarker of ovarian cancer, correlated with Th17 occupancy ratio in patients (P = 0.0068). We found that programmed cell death 1 ligand 1 expression and its associated factors (IL-6 and phospho-signal transducer and activator of transcription 3) were induced by IL-17 in an ovarian cancer cell line. These results suggest that increased Th17 counts and IL-17 level, which correlated with high neutrophil-to-lymphocyte ratio and programmed cell death 1 ligand 1 expression, are potential biomarkers for poor prognosis in ovarian cancer and likely indications for application of programmed cell death 1 ligand 1 pathway inhibitors.


Assuntos
Antígeno B7-H1/genética , Neoplasias do Endométrio/genética , Interleucina-16/metabolismo , Interleucina-17/genética , Neoplasias Ovarianas/genética , Fator de Transcrição STAT3/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Linhagem Celular Tumoral , Neoplasias do Endométrio/imunologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Interleucina-17/metabolismo , Linfócitos Intraepiteliais/metabolismo , Neoplasias Ovarianas/imunologia , Fosforilação , Prognóstico , Células Th17/metabolismo , Regulação para Cima
8.
J Dermatol ; 46(9): 794-797, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31294481

RESUMO

We report a case of kerion celsi due to Trichophyton tonsurans. An 18-year-old male student judo practitioner had alopecic patches, black dots and subcutaneous abscesses on the right temporal region. The damaged hair represented endothrix infection with T. tonsurans, as assessed by mycological examinations. He was treated with oral itraconazole without any therapeutic effect, followed by terbinafine with good effect. A skin biopsy showed neutrophil, lymphocyte and histiocyte infiltration into the dermis and subcutaneous tissue with abscesses around a number of dilated hair follicles. Immunostaining showed that the expression level of human ß-defensin 2 (HBD-2) was decreased in the epidermis of the alopecic and adjacent skin. Because interleukin (IL)-17A generally induces HBD-2 production by epidermal keratinocytes, we also immunohistochemically investigated IL-17A expression. Unexpectedly, many IL-17A-bearing cells were found around destructed hair follicles, indicating that IL-17A expression was not attenuated, but rather increased in the skin lesion. Our case suggests that IL-17A-upregulated antimicrobial peptide expression is disordered in kerion celsi, and severe inflammation with IL-17A may cause tissue damage and resultant scar.


Assuntos
Interleucina-17/metabolismo , Tinha do Couro Cabeludo/imunologia , Trichophyton/imunologia , beta-Defensinas/metabolismo , Adolescente , Biópsia , Folículo Piloso/imunologia , Folículo Piloso/metabolismo , Folículo Piloso/patologia , Humanos , Interleucina-17/imunologia , Masculino , Tinha do Couro Cabeludo/microbiologia , Tinha do Couro Cabeludo/patologia , Trichophyton/isolamento & purificação , beta-Defensinas/imunologia
9.
Exp Parasitol ; 204: 107725, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31306646

RESUMO

Characterisation of the cellular immune response to schistosomiasis is well established for Schistosoma mansoni but a comprehensive description of T cell-mediated immune responses against S. japonicum infection is lacking. Accordingly, 20 CBA mice were infected with cercariae of S. japonicum and the immune response at different time points was determined. Mouse spleen and liver lymphocytes were isolated from the mice and stimulated with schistosomal adult worm antigen preparation (SWAP) and schistosomal soluble egg antigen (SEA). There was a relatively higher Th1 immune response to SWAP compared to SEA at the early phase of infection (up to week 5 post challenge). However, a Th2 immune response directed against SEA was dominant at week 6 post-infection, a time point when the highest IgG response against both SWAP and, especially, SEA was generated. The regulatory immune response was highest at the early phase of the immune response (up to week 5 post challenge) followed by a rapid decline at week 6-post infection. Before egg-laying, S. japonicum induced a regulatory T cell immune response which may limit the early Th1-mediated immune response that is believed to be protective in murine schistosomiasis. Following egg laying, the immune response was polarized to a Th2 immune response mainly directed against the eggs and this may contribute to parasite survival.


Assuntos
Imunidade Celular , Schistosoma japonicum/imunologia , Esquistossomose Japônica/imunologia , Linfócitos T/imunologia , Animais , Antígenos de Helmintos/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Interleucina-17/imunologia , Interleucina-17/metabolismo , Fígado/citologia , Fígado/imunologia , Fígado/parasitologia , Linfócitos/imunologia , Camundongos , Camundongos Endogâmicos CBA , Óvulo/imunologia , Contagem de Ovos de Parasitas , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Caramujos/parasitologia , Baço/citologia , Baço/imunologia , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th2/imunologia
10.
Zhonghua Nei Ke Za Zhi ; 58(6): 419-422, 2019 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-31159519

RESUMO

Objective: To study the significance of Th17 cells in patients with myelodysplastic syndrome (MDS) and iron overload. Methods: A total of 77 patients with MDS admitted to Guangzhou First People's Hospital were enrolled from January 2017 to December 2018,who were divided into iron overload group (37 cases) with serum ferritin (SF) over 1000 µg/L and non-ferrous overload group(40 cases). CD(4)(+)T cells in peripheral blood (PB) and bone marrow (BM) were sorted by flow cytometry. The ratio of Th17 cells and cells with abnormal karyotype were compared. IL-17 and IL-6 protein and RNA expression were detected by ELISA and quantitative real-time PCR(qRT-PCR). Results: The proportions of Th17 cells in PB and BM in iron overload group were significantly higher than those in non-iron overload group [(41.06±0.96)% vs. (26.80±1.21)%; (47.39±1.60)% vs. (34.29±1.03)%; P<0.01]. The Th17 positive cells with abnormal karyotype in iron overload group were more than those in non-iron overload group[(4.96±0.53)% vs. (3.67±0.12)% in PB; (10.06±1.67)% vs. (4.36±0.43)% in BM; P<0.01]. Similarly,the protein levels as well as mRNA expression of IL-6 and IL-17 in patients with iron overload were significantly higher than those in non-iron overload group (P<0.01 both in PB and BM). Conclusions: As hematopoietic regulators secreted by Th17 cells, the expression of IL-6 and IL-17 in MDS patients with iron overload are elevated. This may predict the influence of these factors to the differentiation of Th17 cells.


Assuntos
Interleucina-17/imunologia , Interleucina-6/imunologia , Interleucinas/imunologia , Sobrecarga de Ferro , Síndromes Mielodisplásicas/sangue , Células Th17/imunologia , Medula Óssea , Primers do DNA/genética , Ensaio de Imunoadsorção Enzimática , Ferritinas/sangue , Citometria de Fluxo , Humanos , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Interleucinas/metabolismo , Ferro/sangue , Síndromes Mielodisplásicas/imunologia , RNA , Reação em Cadeia da Polimerase em Tempo Real
11.
World J Microbiol Biotechnol ; 35(6): 94, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31187291

RESUMO

Pseudomonas aeruginosa is the major infectious agent of concern for cystic fibrosis (CF) patients. Therefore, it is necessary to develop appropriate strategies for preventing colonization by this bacterium and/or neutralizing virulence factors. In this study, we formulated the encapsulation of exotoxin A into PLGA nanoparticles. The biological activities of the nanovaccine candidate were also characterized. Based on the results, ETA-PLGA can act as a suitable immunogen to stimulate the humoral and cellular immune response. The antibodies raised against ETA-PLGA significantly decreased bacterial titer in the spleens of the immunized mice after challenge with PAO1 strain, compared to the control groups. The encapsulation of PLGA into ETA led to a significantly higher production of INF-γ, TNF-α, IL-4, and IL-17A cytokine responses compared to the ETA group. ETA-PLGA enhanced IgG responses in immunized mice compared to ETA antigen. We concluded that encapsulation of Pseudomonas aeruginosa ETA to PLGA nanoparticles can increase its functional activity by decreasing the bacterial dissemination.


Assuntos
ADP Ribose Transferases/imunologia , Toxinas Bacterianas/imunologia , Exotoxinas/imunologia , Imunização , Nanoconjugados , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/imunologia , Infecções por Pseudomonas/prevenção & controle , Pseudomonas aeruginosa/patogenicidade , Vacinas Conjugadas , Fatores de Virulência/imunologia , ADP Ribose Transferases/uso terapêutico , Animais , Toxinas Bacterianas/uso terapêutico , Citocinas/metabolismo , Modelos Animais de Doenças , Exotoxinas/uso terapêutico , Feminino , Imunidade Celular , Imunidade Humoral , Imunoglobulina G/sangue , Interferon gama/metabolismo , Interleucina-17/metabolismo , Interleucina-4/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/uso terapêutico , Infecções por Pseudomonas/imunologia , Baço/imunologia , Baço/microbiologia , Fatores de Virulência/uso terapêutico
12.
Cancer Immunol Immunother ; 68(8): 1223-1233, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31201473

RESUMO

Plasmacytoid dendritic cells (pDCs) are present in various primary and metastatic human neoplasms; however, their clinical significance in hepatocellular carcinoma (HCC) is unclear. In this study, we investigated the distribution, prognostic value, and potential function of pDCs in HCC patients undergoing curative resection. We performed immunohistochemical analyses of whole tumor sections from 224 patients to assess the expression of BDCA2, CD3, CD4, CD8, Foxp3, granzyme B, IL-17, and CD34. The findings were validated using tissue microarrays from another two independent cohorts totaling 841 HCC patients undergoing curative resection. Our results demonstrated that high numbers of BDCA2+ pDCs within tumors correlated with high alpha-fetoprotein levels, greater vascular invasion, advanced tumor-node-metastasis stage, shorter overall survival, and a higher recurrence rate. However, patient outcomes were not associated with pDCs in peritumoral stromal or nontumor tissues. Furthermore, an increase in intratumoral pDCs was associated with increased intratumoral infiltration of Foxp3+ regulatory T cells and IL-17-producing cells and correlated with tumor vascular density. Univariate and multivariate analyses revealed that the presence of intratumoral pDCs alone or in combination with regulatory T and/or IL-17-producing cells was an independent predictor of time to recurrence and overall survival. In conclusion, our study demonstrated that intratumoral infiltration by pDCs is a novel indicator for poor prognosis in patients with HCC, possibly through the induction of an immune tolerogenic and inflammatory tumor microenvironment comprising regulatory T and IL-17-producing cells. An assessment of the combination of these cells represents a superior predictor of patient outcome.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Células Dendríticas/imunologia , Interleucina-17/metabolismo , Neoplasias Hepáticas/diagnóstico , Linfócitos T Reguladores/imunologia , Adulto , Idoso , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/mortalidade , Progressão da Doença , Feminino , Seguimentos , Fatores de Transcrição Forkhead/metabolismo , Hepatectomia , Humanos , Lectinas Tipo C/metabolismo , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/mortalidade , Masculino , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Receptores Imunológicos/metabolismo , Análise de Sobrevida , alfa-Fetoproteínas/metabolismo
13.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 54(6): 420-424, 2019 Jun 09.
Artigo em Chinês | MEDLINE | ID: mdl-31177684

RESUMO

Periodontal disease (PD) is an infection-driven chronic inflammatory disease characterized by the inflammation of tooth-supporting tissues and the destruction of the associated alveolar bone. The immune response of the host to periodontal pathogens infection determines the course and progress of the disease. The effects of secreting cytokines interferon-gamma (IFN-γ) and interleukin-17 (IL-17) of T helper 1 cells (Th1) and T helper 17 cells (Th17) on the development of periodontitis has attracted much attention. IFN-γ is a potential immune-modulatory cytokine and can mediate cellular immune responses by activating various immune cells of the host such as macrophages. As one of the most potential bone physiological regulation mediators, IL-17 is closely related with alveolar bone resorption in periodontitis. This review elaborated the relationship between IFN-γ and IL-17 in the progress of periodontitis, providing new explanations into the development of periodontitis and alveolar bone destruction caused by the host immune response.


Assuntos
Perda do Osso Alveolar , Interferon gama , Interleucina-17 , Periodontite , Perda do Osso Alveolar/imunologia , Perda do Osso Alveolar/metabolismo , Humanos , Interferon gama/metabolismo , Interleucina-17/metabolismo , Periodontite/imunologia , Periodontite/metabolismo , Células Th1 , Células Th17
14.
Vet Res ; 50(1): 48, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221216

RESUMO

Enterotoxigenic Escherichia coli (ETEC) are an important cause of post-weaning diarrhea (PWD) in piglets. The IL-17 cytokine family is well known to play important roles in the host defense against bacterial infections at the mucosa. Previously, we reported the potential role of IL-17A in clearing an ETEC infection in piglets. IL-17C, another member of the IL-17 family, is highly expressed in the intestinal epithelium, however, its role during an ETEC infection is still unclear. In this study, we demonstrate that F4+ ETEC induce IL-17C mRNA and protein expression in intestinal tissues as well as in porcine intestinal epithelial cells (IPEC-J2). This IL-17C production is largely dependent on TLR5 signaling in IPEC-J2 cells. Both F4+ ETEC infection and exogenous IL-17C increased the expression of antimicrobial peptides and tight junction proteins, such as porcine beta-defensin (pBD)-2, claudin-1, claudin-2 and occludin in IPEC-J2 cells. Taken together, our data demonstrate that TLR5-mediated IL-17C expression in intestinal epithelial cells enhances mucosal host defense responses in a unique autocrine/paracrine manner in the intestinal epithelium against ETEC infection.


Assuntos
Escherichia coli Enterotoxigênica/fisiologia , Infecções por Escherichia coli/veterinária , Interleucina-17/genética , Doenças dos Suínos/genética , Receptor 5 Toll-Like/genética , Animais , Infecções por Escherichia coli/genética , Infecções por Escherichia coli/metabolismo , Infecções por Escherichia coli/microbiologia , Interleucina-17/metabolismo , Mucosa Intestinal/fisiopatologia , Suínos , Doenças dos Suínos/metabolismo , Doenças dos Suínos/microbiologia , Receptor 5 Toll-Like/metabolismo
15.
Nat Commun ; 10(1): 2162, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31089134

RESUMO

Innate lymphoid cells (ILCs) are crucial for the immune surveillance at mucosal sites. ILCs coordinate early eradication of pathogens and contribute to tissue healing and remodeling, features that are dysfunctional in patients with cystic fibrosis (CF). The mechanisms by which ILCs contribute to CF-immunopathology are ill-defined. Here, we show that group 2 ILCs (ILC2s) transdifferentiated into IL-17-secreting cells in the presence of the epithelial-derived cytokines IL-1ß, IL-23 and TGF-ß. This conversion is abrogated by IL-4 or vitamin D3. IL-17 producing ILC2s induce IL-8 secretion by epithelial cells and their presence in nasal polyps of CF patients is associated with neutrophilia. Our data suggest that ILC2s undergo transdifferentiation in CF nasal polyps in response to local cytokines, which are induced by infectious agents.


Assuntos
Plasticidade Celular/imunologia , Fibrose Cística/imunologia , Inflamação/imunologia , Pólipos Nasais/imunologia , Células Th17/imunologia , Adulto , Animais , Linhagem Celular , Fibrose Cística/sangue , Fibrose Cística/patologia , Feminino , Humanos , Imunidade Inata , Inflamação/sangue , Inflamação/patologia , Interleucina-17/imunologia , Interleucina-17/metabolismo , Interleucina-1beta/imunologia , Interleucina-1beta/metabolismo , Interleucina-23/imunologia , Interleucina-23/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Mucosa Nasal/citologia , Mucosa Nasal/imunologia , Mucosa Nasal/patologia , Pólipos Nasais/sangue , Pólipos Nasais/patologia , Neutrófilos/imunologia , Adulto Jovem
16.
Life Sci ; 229: 46-56, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31085243

RESUMO

AIMS: Tumor growth is an angiogenesis-dependent process that requires sustained new vessel growth. Interleukin-17 (IL-17A) is a key cytokine that modulates tumor progression. However, whether IL-17A affects the metabolism of endothelial cells is unknown. MAIN METHODS: A xenograft model was established by implanting H460 (human lung cancer cell line) cells transfected with IL-17A-expressing or control vector. The effects of IL-17A on sprouting and tube formation of human umbilical vein endothelial cells (HUVECs) were measured. After treatment with IL-17A, the proliferation and migration of HUVECs were examined. Liquid chromatography-mass spectrometry (LC-MS) and Seahorse were used to detect the effects of IL-17A on mitochondrial respiration and fatty acid ß-oxidation (FAO) in HUVECs. Western blotting was used to examine signaling pathways. KEY FINDINGS: Herein, we found that IL-17A promoted H460 tumor growth and angiogenesis in vivo and in vitro. Moreover, IL-17A stimulated angiogenesis by enhancing FAO, increasing mitochondrial respiration of endothelial cells. The AMP-activated protein kinase (AMPK) signaling pathway was activated to promote FAO. Finally, IL-17A-induced angiogenesis was blocked when FAO was inhibited using etomoxir. SIGNIFICANCE: In summary, these results indicate that IL-17A stimulates angiogenesis by promoting FAO. Thus, our study might provide a new therapeutic target for angiogenic vascular disorders.


Assuntos
Ácidos Graxos/química , Células Endoteliais da Veia Umbilical Humana/citologia , Interleucina-17/metabolismo , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/patologia , Neovascularização Patológica/patologia , Animais , Apoptose , Movimento Celular , Proliferação de Células , Feminino , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Camundongos , Camundongos SCID , Neovascularização Patológica/metabolismo , Transdução de Sinais , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Cancer Sci ; 110(7): 2100-2109, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31100180

RESUMO

The presence of interleukin (IL)-17-producing T cells has recently been reported in non-small cell lung cancer (NSCLC) patients. However, the long-term prognostic significance of these populations in NSCLC patients remains unknown. In the present study, we collected peripheral blood from 82 NSCLC patients and 22 normal healthy donors (NC). Percentages of IL-17-producing CD4+ T (Th17), CD8+ T (Tc17) and γδT cells (γδT17) were measured to determine their association with clinical outcomes and overall survival (OS) in NSCLC. All NSCLC patients were followed up until July 2018. Median follow-up time was 13.5 months (range 1-87 months). The 3- and 5-year survival rate was 27% and 19.6%, respectively. We found that Th17 cells and γδT17 cells were significantly increased, whereas Tc17 cells were markedly decreased in patients with NSCLC compared with those in NC. In addition, Th17 cells were significantly positively associated with T helper type 1 cells (Th1), whereas γδT17 cells were significantly negatively associated with γδT + interferon (IFN)-γ+ cells. High percentages of peripheral Tc17 cells were significantly associated with favorable 5-year OS (P = .025), especially in patients with early TNM stage (P = .016). Furthermore, high percentages of peripheral Th17 cells were positively associated with favorable 5-year OS in patients with late TNM stage (P = .002). However, no significant association was observed between γδT17 cells and OS, regardless of the TNM stage. In conclusion, our findings suggest that enhanced Th17 and reduced Tc17 cells in the peripheral blood could be a significant predictor of a favorable prognosis for NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Interleucina-17/metabolismo , Neoplasias Pulmonares/patologia , Linfócitos T/citologia , Células Th17/citologia , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Estudos de Casos e Controles , Feminino , Humanos , Interferon gama/metabolismo , Linfócitos Intraepiteliais/citologia , Linfócitos Intraepiteliais/imunologia , Neoplasias Pulmonares/imunologia , Contagem de Linfócitos , Masculino , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Linfócitos T/imunologia , Células Th1/citologia , Células Th1/imunologia , Células Th17/imunologia
18.
J Dermatol ; 46(6): 482-497, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31062408

RESUMO

The interleukin (IL)-23/IL-17 axis plays a central role in the pathogenesis of psoriasis and is elevated in lesional psoriatic skin. Different murine models have been developed to mimic this pathophysiology each carrying specific merits and limitations. In an attempt to address some of these limitations, B10.RIII mice received a single hydrodynamic injection of IL-23 minicircles (MC) to induce hepatic transcription and the endogenous production of IL-23. Plasma and ear IL-23 levels were dose-dependently (0.3-3 µg) increased in MC injected mice and were sustained over the 14-day study duration. Beginning on day 7 post-injection, mice developed dose-related ear inflammation, histologically confirmed increases in epidermal and dermal area, as well as enhanced neutrophil and macrophage content. Flow cytometry demonstrated increased levels of granulocytes, T cells and monocytes/macrophages in the ear skin, with T cells identified as the main cellular source of IL-17A. Evaluation of mRNA and protein showed time-dependent, increased levels of the IL-23/IL-17 pathway and inflammatory/microbial cytokines/chemokines in the ear which differed kinetically from circulating levels. An anti-IL-23p40 antibody was assessed following both prophylactic administration and administration once the disease was established. Prophylactic dosing completely prevented the development of the ear phenotype across endpoints. Treatment administration showed a dose-related response, with a maximum inhibition of 64-94%, depending on endpoint. These data demonstrate that the IL-23 MC model is a useful approach to study IL-23/IL-17-driven skin inflammation and may facilitate preclinical assessment of novel therapies.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Interleucina-17/imunologia , Interleucina-23/imunologia , Psoríase/imunologia , Animais , DNA Circular/administração & dosagem , DNA Circular/genética , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Técnicas de Transferência de Genes , Humanos , Interleucina-17/metabolismo , Interleucina-23/antagonistas & inibidores , Interleucina-23/genética , Masculino , Camundongos , Psoríase/sangue , Psoríase/tratamento farmacológico , Psoríase/patologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Pele/imunologia , Pele/patologia , Resultado do Tratamento
19.
Iran J Allergy Asthma Immunol ; 18(2): 163-172, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31066252

RESUMO

Unexplained infertility (UI) is one of the most common diagnoses in the fertility care. Seminal plasma (SP) plays a crucial role in the regulation of female immune responses and the success of a pregnancy. In vitro fertilization (IVF) is a well-known method for the treatment of UI. In this study, we aimed to investigate the effect of SP on the differentiation of T helper (Th) cell subsets and the relationship between these subsets with the rate of IVF success in a group of women complicated with UI compared to those with normal pregnancy. This study was conducted on 20 UI couples (ten with successful and ten with unsuccessful IVF outcome) and 10 fertile couples as the control group. Four color flow cytometry technique was used to detect Th cell subsets in the peripheral blood mononuclear cells (PBMC) with or without stimulation by SP. Results indicated that the frequencies of IL-17+ and Foxp3+ T cells after incubation with SP was significantly increased in couples with unsuccessful IVF outcome as compared to successful and healthy groups (p<0.05). Additionally, a positive correlation was observed between Th1 and Th2 cells in the unsuccessful IVF group (R=0.6, p=0.03). In summary, the results of the present study demonstrated that exposure to SP might increase Th17 and Treg cell frequencies in infertile women with unsuccessful IVF, and might also balance inflammatory to regulatory responses to finally tune-up the Th1/Th2/Th17/Treg balance and support the success of IVF.


Assuntos
Fertilização In Vitro/métodos , Infertilidade Feminina/imunologia , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th17/imunologia , Células Th2/imunologia , Adulto , Biomarcadores , Células Cultivadas , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Imunofenotipagem , Infertilidade Feminina/diagnóstico , Interleucina-17/metabolismo , Masculino , Prognóstico , Sêmen/metabolismo , Resultado do Tratamento
20.
Food Chem Toxicol ; 129: 365-375, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31054998

RESUMO

Ferulic acid (FA), a phenolic phytochemical, is commonly found in grains, vegetables, and fruits. Interleukin-17A (IL-17A) and IL-17 receptor A (IL-17RA) interaction is one of important therapeutic targets for psoriasis. Here we analyzed the FA effects on IL-17A/IL-17RA interaction and psoriasis-like skin injury induced by imiquimod (IMQ). IL-17A-blocking assay and docking analysis showed that FA interacted with Trp-67, Gln-94, and Glu-95 residues of IL-17A via hydrogen bonds and consequently abolished the binding of IL-17RA to IL-17A. Mice were topically given with IMQ and orally given with various amounts of FA for 14 consecutive days. FA attenuated IMQ-induced psoriasis-like skin lesions in a dose-dependent manner, and the epidermal thickness of mice treated with 100 mg/kg FA was reduced by 53.48 ±â€¯4.44% in comparison with sham. Global analysis of differentially expressed genes showed that IMQ and FA significantly affected immune response, metabolism, and mitogen-activated protein kinase signaling pathways. Immunohistochemical staining showed that FA inhibited the infiltration and the cytokine secretion of Th17 cell, dendritic cell, and granulocyte subsets in psoriatic skin tissues. In conclusion, we newly identified that oral administration of FA protected against IMQ-induced psoriatic skin injury in mice. Moreover, its protection was associated with the interference of IL-17A/IL-17RA interaction.


Assuntos
Adjuvantes Imunológicos/toxicidade , Ácidos Cumáricos/farmacologia , Imiquimode/toxicidade , Interleucina-17/metabolismo , Psoríase/induzido quimicamente , Psoríase/prevenção & controle , Receptores de Interleucina-17/metabolismo , Animais , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Ligação Proteica
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