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1.
Life Sci ; 248: 117456, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32097666

RESUMO

AIMS: In this study, we will investigate the therapeutic effects of berberine (BBR) in Helicobacter pylori (H. pylori) induced chronic atrophic gastritis (CAG). Furthermore, potential mechanisms of BBR in regulating IRF8-IFN-γ signaling axis will also be investigated. MATERIALS AND METHODS: H. pylori were utilized to establish CAG model of rats. Therapeutic effects of BBR on serum supernatant indices, and histopathology of stomach were analyzed in vivo. Moreover, GES-1 cells were infected by H. pylori, and intervened with BBR in vitro. Cell viability, morphology, proliferation, and quantitative analysis were detected by high-content screening (HCS) imaging assay. To further investigate the potential mechanisms of BBR, relative mRNA, immunohistochemistry and protein expression in IRF8-IFN-γ signaling axis were measured. KEY FINDINGS: Results showed serum supernatant indices including IL-17, CXCL1, and CXCL9 were downregulated by BBR intervention, while, G-17 increased significantly. Histological injuries of gastric mucosa induced by H. pylori also were alleviated. Moreover, cell viability and morphology changes of GES-1 cells were improved by BBR intervention. In addition, proinflammatory genes and IRF8-IFN-γ signaling axis related genes, including Ifit3, Upp1, USP18, Nlrc5, were suppressed by BBR administration in vitro and in vivo. The proteins expression related to IRF8-IFN-γ signaling axis, including Ifit3, IRF1 and Ifit1 were downregulated by BBR intervention.


Assuntos
Anti-Inflamatórios/farmacologia , Berberina/farmacologia , Gastrite Atrófica/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Fatores Reguladores de Interferon/genética , Interferon gama/genética , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quimiocina CXCL1/antagonistas & inibidores , Quimiocina CXCL1/genética , Quimiocina CXCL1/imunologia , Quimiocina CXCL9/antagonistas & inibidores , Quimiocina CXCL9/genética , Quimiocina CXCL9/imunologia , Doença Crônica , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Gastrite Atrófica/genética , Gastrite Atrófica/imunologia , Gastrite Atrófica/microbiologia , Regulação da Expressão Gênica , Infecções por Helicobacter/genética , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/crescimento & desenvolvimento , Helicobacter pylori/patogenicidade , Humanos , Fatores Reguladores de Interferon/antagonistas & inibidores , Fatores Reguladores de Interferon/imunologia , Interferon gama/antagonistas & inibidores , Interferon gama/imunologia , Interleucina-17/agonistas , Interleucina-17/genética , Interleucina-17/imunologia , Masculino , Proteínas NLR/antagonistas & inibidores , Proteínas NLR/genética , Proteínas NLR/imunologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Uridina Fosforilase/antagonistas & inibidores , Uridina Fosforilase/genética , Uridina Fosforilase/imunologia
2.
Biol Pharm Bull ; 41(2): 182-189, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29386478

RESUMO

Interleukin (IL)-19 is a member of the IL-10 family of interleukins and is an immuno-modulatory cytokine produced by the main macrophages. The gastrointestinal tissues of IL-19 knockout mice show exacerbated experimental colitis mediated by the innate immune system and T cells. There is an increasing focus on the interaction and relationship of IL-19 with the function of T cells. Contact hypersensitivity (CHS) is T cell-mediated cutaneous inflammation. Therefore, we asked whether IL-19 causes CHS. We investigated the immunological role of IL-19 in CHS induced by 1-fluoro-2,4-dinitrofluorobenzene as a hapten. IL-19 was highly expressed in skin exposed to the hapten, and ear swelling was increased in IL-19 knockout mice. The exacerbation of the CHS response in IL-19 knockout mice correlated with increased levels of IL-17 and IL-6, but no alterations were noted in the production of interferon (IFN)γ and IL-4 in the T cells of the lymph nodes. In addition to the effect on T cell response, IL-19 knockout mice increased production of inflammatory cytokines. These results show that IL-19 suppressed hapten-dependent skin inflammation in the elicitation phase of CHS.


Assuntos
Dermatite de Contato/metabolismo , Interleucinas/agonistas , Linfonodos/metabolismo , Pele/metabolismo , Animais , Células Cultivadas , Dermatite de Contato/sangue , Dermatite de Contato/imunologia , Dermatite de Contato/patologia , Dinitrofluorbenzeno/análogos & derivados , Dinitrofluorbenzeno/toxicidade , Orelha , Regulação da Expressão Gênica/efeitos dos fármacos , Haptenos/toxicidade , Imunidade Inata/efeitos dos fármacos , Imuno-Histoquímica , Interleucina-10 , Interleucina-17/agonistas , Interleucina-17/genética , Interleucina-17/metabolismo , Interleucina-6/agonistas , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucinas/sangue , Interleucinas/genética , Interleucinas/metabolismo , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Linfonodos/patologia , Camundongos Endogâmicos BALB C , Camundongos Knockout , RNA Mensageiro/metabolismo , Pele/efeitos dos fármacos , Pele/imunologia , Pele/patologia , Baço/efeitos dos fármacos , Baço/imunologia , Baço/metabolismo , Baço/patologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Linfócitos T/patologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th1/metabolismo , Células Th1/patologia
3.
Immunotherapy ; 9(12): 963-978, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28879789

RESUMO

Psoriasis is a chronic immune-mediated skin disorder affecting approximately 2-3% of the worldwide population. Recent advances in our understanding of the immunopathogenesis of psoriasis have resulted in novel therapeutic agents. IL-17, a pro-inflammatory cytokine, plays a pivotal role in psoriasis. Therapeutic agents targeting this cytokine have shown clinical effectiveness in the treatment of moderate-to-severe plaque psoriasis. Brodalumab, a human antibody against IL-17 receptor A, has been approved by the US FDA in February 2017, by the Japanese Pharmaceuticals and Medical Devices Agency in July 2016 and by the EMA in July 2017 for the treatment of moderate-to-severe psoriasis. This article reviews the published data relating to brodalumab for the treatment of moderate-to-severe plaque psoriasis.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Imunoterapia/métodos , Interleucina-17/metabolismo , Psoríase/terapia , Animais , Anticorpos Monoclonais Humanizados , Carcinogênese , Citocinas/metabolismo , Progressão da Doença , Humanos , Interleucina-17/agonistas , Psoríase/imunologia , Resultado do Tratamento
4.
J Immunol ; 183(8): 5350-7, 2009 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-19786547

RESUMO

TNF-like ligand 1A (TL1A), a member of the TNF superfamily, is the ligand of DR3 and DcR3. Several types of cells, such as endothelial cells, monocytes/macrophages, dendritic cells, and CD4 and CD8 T cells, are capable of producing this cytokine. In present study, we demonstrated that TL1A aggravated collagen-induced arthritis in mice. It increased collagen-induced arthritis penetrance and clinical scores as well as the severity of the pathological findings. TL1A administration led to the occurrence of multiple enlarged germinal centers in the spleen, and it boosted serum anti-collagen Ab titers in vivo. In vitro, TL1A augmented TNF-alpha production by T cells upon TCR ligation, and it greatly enhanced Th17 differentiation and IL-17 production. We further showed that human rheumatoid arthritis (RA) synovial fluids had elevated TL1A titers, and human chrondrocytes and synovial fibroblasts were capable of secreting TL1A upon TNF-alpha or IL-1beta stimulation. Taken together, these data suggest that TL1A secretion in lymphoid organs might contribute to RA initiation by promoting autoantibody production, and TL1A secretion stimulated by inflammatory cytokines in RA joints might be a part of a vicious circle that aggravates RA pathogenesis.


Assuntos
Artrite Reumatoide/imunologia , Linfócitos T/imunologia , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/imunologia , Animais , Artrite Reumatoide/induzido quimicamente , Autoanticorpos/sangue , Autoanticorpos/efeitos dos fármacos , Células Cultivadas , Condrócitos/imunologia , Condrócitos/metabolismo , Colágeno Tipo II/farmacologia , Fibroblastos/imunologia , Fibroblastos/metabolismo , Centro Germinativo/efeitos dos fármacos , Centro Germinativo/imunologia , Centro Germinativo/metabolismo , Humanos , Interleucina-17/agonistas , Interleucina-17/biossíntese , Interleucina-17/imunologia , Interleucina-1beta/farmacologia , Articulações/imunologia , Articulações/patologia , Masculino , Camundongos , Camundongos Endogâmicos DBA , Proteínas Recombinantes/farmacologia , Baço/efeitos dos fármacos , Baço/imunologia , Baço/metabolismo , Líquido Sinovial/imunologia , Líquido Sinovial/metabolismo , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/farmacologia , Fator de Necrose Tumoral alfa/agonistas , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/farmacologia
5.
Immunol Lett ; 123(2): 155-9, 2009 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-19428564

RESUMO

Cathepsins of the cysteine, aspartyl, and serine classes are involved in antigen processing in the class II major histocompatibility complex (MHC) loading compartment. Investigation of these proteases in living cells is difficult to perform due to the lack of highly specific cell-permeable inhibitors. Recently, a highly selective cathepsin B (CatB) inhibitor, Z-Arg-Leu-Arg-alpha-aza-glycyl-Ile-Val-OMe (ZRLR), was described. We found that ZRLR is cell-permeable and specifically inhibits CatB, in contrast to the CatB inhibitor, CA074-OMe, which blocks cysteine cathepsins in addition to CatB in primary human antigen-presenting cells (APC). Furthermore, we compared both CA074-OMe and ZRLR in the ability to alter tetanus toxin C-fragment (TTC) presentation to T cells by different APC. As a result, we found enhanced presentation of TTC in the presence of ZRLR, as determined by detection of pro-inflammatory cytokines. We conclude that ZRLR is a specific, cell-permeable CatB inhibitor which can be used for antigen presenting studies in situ.


Assuntos
Catepsina B/antagonistas & inibidores , Permeabilidade da Membrana Celular , Inibidores de Cisteína Proteinase/farmacocinética , Células Dendríticas/imunologia , Oligopeptídeos/farmacocinética , Fragmentos de Peptídeos/imunologia , Toxina Tetânica/imunologia , Apresentação de Antígeno/efeitos dos fármacos , Catepsina B/metabolismo , Inibidores de Cisteína Proteinase/química , Inibidores de Cisteína Proteinase/farmacologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/enzimologia , Dipeptídeos/farmacologia , Humanos , Interferon gama/agonistas , Interferon gama/biossíntese , Interferon gama/imunologia , Interleucina-17/agonistas , Interleucina-17/biossíntese , Interleucina-17/imunologia , Oligopeptídeos/química , Oligopeptídeos/farmacologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/agonistas , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/imunologia
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