RESUMO
Inflammation is a basal host defense response that eliminates the causes and consequences of infection and tissue injury. Macrophages are the primary immune cells involved in the inflammatory response. When activated by LPS, macrophages release various pro-inflammatory cytokines, chemokines, inflammatory mediators, and MMPs. However, unbridled inflammation causes further damage to tissues. Safinamide is a selective and reversible monoamine oxidase B (MAOB) inhibitor that has been used for the treatment of Parkinson's disease. In this study, we aimed to investigate whether safinamide has effects on LPS-treated macrophages. Our results show that safinamide inhibited the expression of pro-inflammatory cytokines such as IL-1α, TNF-α, and IL-6. Furthermore, safinamide suppressed the production of CXCL1 and CCL2, thereby preventing leukocyte migration. In addition, safinamide reduced iNOS-derived NO, COX-2-derived PGE2, MMP-2, and MMP-9. Importantly, the functions of safinamide mentioned above were found to be dependent on its inhibitory effect on the TLR4/NF-κB signaling pathway. Our data indicates that safinamide may exert a protective effect against inflammatory response.
Assuntos
Alanina/análogos & derivados , Anti-Inflamatórios/farmacologia , Benzilaminas/farmacologia , Inflamação/prevenção & controle , Macrófagos/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/antagonistas & inibidores , Alanina/farmacologia , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Dinoprostona/metabolismo , Humanos , Inflamação/induzido quimicamente , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Células U937RESUMO
OBJECTIVE: To explore the role of neuregulin (neural regulation of protein, NRG) in the process of mouse spermatogonia proliferation. METHODS: Mouse testis fragments were cultured in the medium DMEM containing purified NRG1beta or NRG3 at the concentration of 50, 100 and 200 ng/ml, respectively, followed by BrdU immunohistochemical staining and determination of the proliferation rate of spermatogonia. RESULTS: Compared with the control group, neuregulin significantly promoted the proliferation of spermatogonia (P < 0.05). The proliferation rates of spermatogonia cultured in the medium with 50, 100 and 200 ng/ml of NRG13 were 1.69, 1.55 and 1.86 times, and those with 50, 100 and 200 ng/ml of NRG3 were 1.35, 1.54 and 2.11 times that of the control. CONCLUSION: NRG1beta and NRG3 can promote the proliferation of mouse spermatogonia, and NRG is expected to be applied in the treatment of male infertility.
