“…Consistently, another study showed that coumarins reduced the expression of MHC II, CD86 and T-bet, as well as the production of IL-12, which may promote the generation of CD4 þ CD25 þ Foxp3 þ Tregs. Importantly, coumarins decreased the clinical arthritis score and paw swelling and protected tissues against bone destruction in type II collagen induced arthritis mice, which was associated with a substantial decrease in the production of IFN-γ and IL-2, and an increase of IL-10 and TGF-β (Luo et al, 2011). Further, coumarins down regulated the expression of TLR4 and the downstream signaling molecules, including myeloid differentiation factor (MyD)88, NF-κB, IL-1β, Toll-IL-1 receptor domain-containing adaptor inducing interferon-β (TRIF), TRIF-related adaptor molecule (TRAM), interferon regulatory factor (IRF)-3 and IFN-β, suggesting that coumarins inhibit both MyD88-dependent and -independent pathways of TLR4 .…”