Abstract: We hypothesized whether systemic administration of high-molecular-weight hyaluronic acid (HMW HA) could rescue trinitrobenzene sulfonic acid (TNBS)-induced colitis through Toll-like receptor 4 (TLR4) signal. C3H/HeN mice and C3H/HeJ mice were used. Mice were divided into four groups: control, 50% ethanol treatment group, TNBS treatment group, and TNBS plus HA treatment group. The weight changes, clinical scores, macroscopic scores, and histological scores were recorded. Cyclooxygenase 2 (Cox-2) and prostaglandin E₂ (PGE₂) expressions were measured both in colons and peritoneal macrophages from these mice. HA was a rescue therapy for the colitis induced by TNBS only in C3H/HeN mice. The clinical score, macroscopic score, and histological score were much lower in C3H/HeN mice receiving TNBS plus HA treatment. Cox-2 and PGE₂ expressions only increased in C3H/HeN mice. These Cox-2 expressing cells were macrophages. HA can also promote the production of Cox-2 and PGE₂ in peritoneal macrophages from C3H/HeN mice. Our data demonstrated that HMW HA can rescue TNBS-induced colitis through inducing Cox-2 and PGE₂ expressions in a TLR4-dependent way. Macrophages may be the effector cells of HMW HA.

Key words: Trinitrobenzene sulfonic acid (TNBS) colitis, Therapy, Hyaluronic acid, Toll-like receptor

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