Department of Gastroenterology, West China Hospital of Sichuan University, Chengdu, China.
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.
我们假设全身性给予高分子量透明质酸(HMW HA)是否能通过 Toll 样受体 4(TLR4)信号拯救三硝基苯磺酸(TNBS)诱导的结肠炎。使用 C3H/HeN 小鼠和 C3H/HeJ 小鼠。将小鼠分为四组:对照组、50%乙醇处理组、TNBS 处理组和 TNBS 加 HA 处理组。记录体重变化、临床评分、宏观评分和组织学评分。测量这些小鼠结肠和腹腔巨噬细胞中环氧化酶 2(Cox-2)和前列腺素 E(PGE(2))的表达。HA 仅在 C3H/HeN 小鼠中是 TNBS 诱导的结肠炎的挽救治疗。接受 TNBS 加 HA 治疗的 C3H/HeN 小鼠的临床评分、宏观评分和组织学评分要低得多。仅在 C3H/HeN 小鼠中 Cox-2 和 PGE(2)的表达增加。这些 Cox-2 表达细胞是巨噬细胞。HA 还可以促进 C3H/HeN 小鼠腹腔巨噬细胞中 Cox-2 和 PGE(2)的产生。我们的数据表明,HMW HA 可以通过 TLR4 依赖性诱导 Cox-2 和 PGE(2)的表达来挽救 TNBS 诱导的结肠炎。巨噬细胞可能是 HMW HA 的效应细胞。