Biomedicine & Pharmacotherapy (Sep 2020)
Astilbin combined with lipopolysaccharide induces IL-10-producing regulatory B cells via the STAT3 signalling pathway
Abstract
Objectives: Astilbin exerts immunoregulatory activities and plays anti-inflammatory effects in inflammation-associated diseases. IL-10-producing B cells are the major subset of regulatory B cells (Bregs) and inhibit inflammation and autoimmune diseases. This study aimed to analyse the inducing effect of astilbin on Bregs and investigate the involved molecular mechanisms. Methods: The frequencies and activities of IL-10-producing Bregs were observed using the co-treatment of astilbin and lipopolysaccharide (LPS) ex vivo. The protective effect of astilbin/LPS-induced Bregs on dextran sulphate sodium (DSS)-induced colitis was confirmed in vivo. The molecular signalling events of Breg induction were checked via Western blot. CD40−/− and toll-like receptor (TLR) 4−/− B cells were treated with astilbin/LPS to determine the modulatory role of CD40 or TLR4 on astilbin/LPS-induced Bregs. Results: Although astilbin alone could not affect Bregs, the co-treatment of astilbin and LPS remarkably induced CD19+ CD1dhi and CD19+ TIM-1+ cells which produced IL-10 ex vivo. Colonic CD19+ CD1dhi and CD19+ TIM-1+ cells were also increased in astilbin-treated mice with DSS-induced colitis. The adoptive transfer of CD19+ TIM-1+ cells pre-induced by astilbin/LPS directly suppressed the progression of DSS-induced colitis. Combined astilbin and LPS stimulated the STAT3 activation of CD19+ TIM-1+ cells but had no effects on SOCS3, AKT, NF-κB, Erk, JNK nor P38. Inhibiting the STAT3 phosphorylation of CD19+ TIM-1+ cells abolished Breg induction by astilbin/LPS. Furthermore, Breg induction was weakened in CD40−/− B cells with the decrease in STAT3 activation, but had disappeared in TLR4−/− B cells with no STAT3 activation, thereby confirming the indispensable role of TLR4 signalling in the induction of IL-10-producing Bregs. Conclusions: This study reports the new immunoregulatory role of astilbin for promoting IL-10-producing B cells and suggests the possible use of astilbin in the therapy of inflammatory diseases.
