RESUMO
Human amniotic membrane-derived mesenchymal stem cells (hAM-MSCs) are capable of differentiating into several lineages and possess immunomodulatory properties. In this study, we investigated the soluble factor-mediated immunomodulatory effects of hAM-MSCs. Mitogen-induced peripheral blood mononuclear cell (PBMC) proliferation was suppressed by hAM-MSCs in a dose-dependent manner as well as hAM-MSC culture supernatant. Moreover, interferon-gamma and interleukin (IL)-17 production significantly decreased from PBMC, whereas IL-10 from PBMCs and transforming growth factor beta (TGF-beta) production from hAM-MSCs significantly increased in co-cultures of hAM-MSCs and PBMCs. Production of several MSC factors, including hepatocyte growth factor (HGF), TGF-beta, prostaglandin E2 (PGE2), and indoleamine 2, 3 dioxygenase (IDO), increased significantly in hAM-MSCs co-cultured with PBMCs. These results indicate that the immunomodulatory effects of hAM-MSCs may be associated with soluble factors (TGF-beta, HGF, PGE2, and IDO), suggesting that hAM-MSCs may have potential clinical use in regenerative medicine.
Assuntos
Feminino , Humanos , Gravidez , Âmnio/citologia , Diferenciação Celular/imunologia , Técnicas de Cocultura , Dinoprostona/genética , Fator de Crescimento de Hepatócito/genética , Fatores Imunológicos/imunologia , Imunofenotipagem , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Interferon gama/imunologia , Interleucina-10/análise , Interleucina-17/análise , Leucócitos Mononucleares/citologia , Células-Tronco Mesenquimais/citologia , RNA Mensageiro/química , Medicina Regenerativa/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Crescimento Transformador beta/genéticaRESUMO
The anti-inflammatory effects of an ethanol extract of Angelica gigas (EAG) were investigated in vitro and in vivo using croton oil-induced inflammation models. Croton oil (20 microgram/mL) up-regulated mRNA expression of cyclooxygenase (COX)-I and COX-II in the macrophage cell line, RAW 264.7, resulting in the release of high concentrations of prostaglandin E2 (PGE2). EAG (1~10 microgram/mL) markedly suppressed croton oil-induced COX-II mRNA expression and PGE2 production. Application of croton oil (5% in acetone) to mouse ears caused severe local erythema, edema and vascular leakage, which were significantly attenuated by oral pre-treatment with EAG (50~500 mg/kg). Croton oil dramatically increased blood levels of interleukin (IL)-6 and PGE2 without affecting tumor-necrosis factor (TNF)-alpha and nitric oxide (NO) levels. EAG pre-treatment remarkably lowered IL-6 and PGE2, but did not alter TNF-alpha or NO concentrations. These results indicate that EAG attenuates inflammatory responses in part by blocking the COX-PGE2 pathway. Therefore, EAG could be a promising candidate for the treatment of inflammatory diseases.