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Hyaluronic acid as a rescue therapy for trinitrobenzene sulfonic acid-induced colitis through Cox-2 and PGE_2 in a Toll-like receptor 4-dependent way

Huan CHEN,Mahesh MAHASETH,Yan ZHANG(Department of Gastroenterology,West China Hospital of Sichuan University,Chengdu 610041,China)  
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 E 2(PGE 2) 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 PGE 2 expressions only increased in C3H/HeN mice.These Cox-2 expressing cells were macrophages.HA can also promote the production of Cox-2 and PGE 2 in peritoneal macrophages from C3H/HeN mice.Our data demonstrated that HMW HA can rescue TNBS-induced colitis through inducing Cox-2 and PGE 2 expressions in a TLR4-dependent way.Macrophages may be the effector cells of HMW HA.
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