Hyaluronic acid as a rescue therapy for trinitrobenzene sulfonic acid-induced colitis through Cox-2 and PGE2 in a Toll-like receptor 4-dependent way

J Zhejiang Univ Sci B. 2011 Sep;12(9):712-9. doi: 10.1631/jzus.B1000362.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colitis / drug therapy*
  • Cyclooxygenase 2 / metabolism*
  • Dinoprostone / metabolism*
  • Female
  • Hyaluronic Acid / chemistry
  • Hyaluronic Acid / pharmacology*
  • Immunohistochemistry / methods
  • Macrophages, Peritoneal / cytology
  • Mice
  • Mice, Inbred C3H
  • Microscopy, Fluorescence / methods
  • Toll-Like Receptor 4 / metabolism*
  • Toll-Like Receptors / metabolism
  • Treatment Outcome
  • Trinitrobenzenesulfonic Acid / pharmacology*


  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Trinitrobenzenesulfonic Acid
  • Hyaluronic Acid
  • Cyclooxygenase 2
  • Dinoprostone