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.
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Bai, K.J., Spicer, A.P., Mascarenhas, M.M., Yu, L., Ochoa, C.D., Garg, H.G., Quinn, D.A., 2005. The role of hyaluronan synthase 3 in ventilator induced lung injury. Am. J. Respir. Crit. Care Med., 172(1):92–98. [doi:10.1164/rccm.200405-652OC]
Boodoo, S., Spannhake, E.W., Powell, J.D., Horton, M.R., 2006. Differential regulation of hyaluronan-induced IL-8 and IP-10 in airway epithelial cells. AJP Lung Cell. Mol. Physiol., 291(3):L479–L486. [doi:10.1152/ajplung.00518.2005]
Breborowicz, A., Połubinska, A., Moberly, J., Ogle, K., Martis, L., Oreopoulos, D., 2001. Hyaluronan modifies inflammatory response and peritoneal permeability during peritonitis in rats. Am. J. Kidney Dis., 37(3):594–600. [doi:10.1016/S0272-6386(01)80018-4]
Collins, C.B., Ho, J., Wilson, T.E., Wermers, J.D., Tlaxca, J.L., Lawrence, M.B., Solga, M., Lannigan, J., Rivera-Nieves, J., 2008. CD44 deficiency attenuates chronic murine ileitis. Gastroenterology, 135(6):1993–2002. [doi:10.1053/j.gastro.2008.08.053]
de la Motte, C.A., Hascall, V.C., Calabro, A., Yen-Lieberman, B., Strong, S.A., 1999. Mononuclear leukocytes preferentially bind via CD44 to hyaluronan on human intestinal mucosal smooth muscle cells after virus infection or treatment with poly(I.C). J. Biol. Chem., 274(43): 30747–30755. [doi:10.1074/jbc.274.43.30747]
Deng, J.F., Geng, L., Qian, Y.G., Li, H., Wang, Y., Xie, H.Y., Feng, X.W., Zheng, S.S., 2007. The role of Toll-like receptors 2 and 4 in acute allograft rejection after liver transplantation. Transplant. Proc., 39(10):3222–3224. [doi:10.1016/j.transproceed.2007.02.102]
Földes, G., von Haehling, S., Okonko, D.O., Jankowska, E.A., Poole-Wilson, P.A., Anker, S.D., 2008. Fluvastatin reduces increased blood monocyte Toll-like receptor 4 expression in whole blood from patients with chronic heart failure. Int. J. Cardiol., 124(1):80–85. [doi:10.1016/j.ijcard.2006.12.024]
Fukata, M., Chen, A., Klepper, A., Krishnareddy, S., Vamadevan, A.S., Thomas, L.S., Xu, R., Inoue, H., Arditi, M., Dannenberg, A.J., et al., 2006. Cox-2 is regulated by Toll-like receptor-4 (TLR4) signaling: role in proliferation and apoptosis in the intestine. Gastroenterology, 131(3):862–877. [doi:10.1053/j.gastro.2006.06.017]
Horton, M.R., McKee, C.M., Bao, C., Liao, F., Farber, J.M., Hodge-DuFour, J., Puré, E., Oliver, B.L., Wright, T.M., Noble, P.W., 1998. Hyaluronan fragments synergize with interferon-γ to induce the C-X-C chemokines Mig and interferon-inducible protein-10 in mouse macrophages. J. Biol. Chem., 273(52):35088–35094. [doi:10.1074/jbc.273.52.35088]
Horton, M.R., Shapiro, S., Bao, C., Lowenstein, C.J., Noble, P.W., 1999. Induction and regulation of macrophage metalloelastase by hyaluronan fragments in mouse macrophages. J. Immunol., 162(7):4171–4176.
Itano, N., Sawani, T., Yoshida, M., Lenas, P., Yamada, Y., Imagawa, M., Shinomura, T., Hamaguchi, M., Yoshida, Y., Ohnuki, Y., et al., 1999. Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties. J. Biol. Chem., 274(35):25085–25092. [doi:10.1074/jbc.274.35.25085]
Janeway, C.A., Medzhitov, R., 1999. Lipoproteins take their toll on the host. Curr. Biol., 9(23):R879–R882. [doi:10.1016/S0960-9822(00)80073-1]
Jiang, D., Liang, J., Fan, J., Yu, S., Chen, S., Luo, Y., Prestwich, G.D., Mascarenhas, M.M., Garg, H.G., Quinn, D.A., et al., 2005. Regulation of lung injury and repair by Toll-like receptors and hyaluronan. Nat. Med., 11(11): 1173–1179. [doi:10.1038/nm1315]
Lahat, G., Halperin, D., Barazovsky, E.L., Shalit, I., Rabau, M., Klausner, J., Fabian, I., 2007. Immunomodulatory effects of ciprofloxacin in TNBS-induced colitis in mice. Inflamm. Bowel Dis., 13(5):557–565. [doi:10.1002/ibd.20077]
Liu, Y.Y., Lee, C.H., Dedaj, R., Zhao, H., Mrabat, H., Sheidlin, A., Syrkina, O., Huang, P.M., Garg, H.G., Hales, C.A., et al., 2008. High-molecular-weight hyaluronan—a possible new treatment for sepsis-induced lung injury: a preclinical study in mechanically ventilated rats. Crit. Care, 12(4):R102. [doi:10.1186/cc6982]
Majors, A.K., Austin, R.C., de la Motte, C.A., Pyeritz, R.E., Hascall, V.C., Kessler, S.P., Sen, G., Strong, S.A., 2003. Endoplasmic reticulum stress induces hyaluronan deposition and leukocyte adhesion. J. Biol. Chem., 278(47): 47223–47231. [doi:10.1074/jbc.M304871200]
Mascarenhas, M.M., Day, R.M., Ochoa, C.D., Choi, W.I., Yu, L., Ouyang, B., Garg, H.G., Hales, C.A., Quinn, D.A., 2004. Low molecular weight hyaluronan from stretched lung enhances IL-8 expression. Am. J. Respir. Cell Mol. Biol., 30(1):51–60. [doi:10.1165/rcmb.2002-0167OC]
McKee, C.M., Lowenstein, C.J., Horton, M.R., Wu, J., Bao, C., Chin, B.Y., Choi, A.M., Noble, P.W., 1997. Hyaluronan fragments induce nitric-oxide synthase in murine macrophages through a nuclear factor κB-dependent mechanism. J. Biol. Chem., 272(12):8013–8018. [doi:10.1074/jbc.272.12.8013]
Noble, P.W., McKee, C.M., Cowman, M., Shin, H.S., 1996. Hyaluronan fragments activate an NF-κB/I-κBα autoregulatory loop in murine macrophages. J. Exp. Med., 183(5):2373–2378. [doi:10.1084/jem.183.5.2373]
Połubinska, A., Pawlaczyk, K., Kużlan-Pawlaczyk, M., Wieczorowska-Tobis, K., Chen, C., Moberly, J.B., Martis, L., Breborowicz, A., Oreopoulos, D.G., 2000. Dialysis solution containing hyaluronan: effect on peritoneal permeability and inflammation in rats. Kidney Int., 57(3): 1182–1189. [doi:10.1046/j.1523-1755.2000.00946.x]
Spicer, A.P., McDonald, J.A., 1998. Characterization and molecular evolution of a vertebrate hyaluronan synthase gene family. J. Biol. Chem., 273(4):1923–1932. [doi:10.1074/jbc.273.4.1923]
Taylor, K.R., Yamasaki, K., Radek, K.A., di Nardo, A., Goodarzi, H., Golenbock, D., Beutler, B., Gallo, R.L., 2007. Recognition of hayluronan released in sterile injury involves a unique receptor complex dependent on Toll-like receptor 4, CD44, and MD-2. J. Biol. Chem., 282(25):18265–18275. [doi:10.1074/jbc.M606352200]
Wallet, M.A., Wallet, S.M., Guiulfo, G., Sleasman, J.W., Goodenow, M.M., 2010. IFN-γ primes macrophages for inflammatory activation by high molecular weight hyaluronan. Cell. Immunol., 262(2):84–88. [doi:10.1016/j. cellimm.2010.02.013]
Wang, C.T., Lin, Y.T., Chiang, B.L., Lin, Y.H., Hou, S.M., 2006. Weight hyaluronic acid down-regulates the gene expression of osteoarthritis-associated cytokines and enzymes in fibroblast-like synoviocytes from patients with early osteoarthritis. Osteoarthritis and Cartilage, 14(12):1237–1247. [doi:10.1016/j.joca.2006.05.009]
Wang, M.J., Kuo, J.S., Lee, W.W., Huang, H.Y., Chen, W.F., Lin, S.Z., 2006. Translational event mediates differential production of tumor necrosis factor-α in hyaluronanstimulated microglia and macrophages. J. Neurochem., 97(3):857–871. [doi:10.1111/j.1471-4159.2006.03776.x]
Zhang, X., Shan, P., Qureshi, S., Homer, R., Medzhitov, R., Noble, P.W., Lee, P.J., 2005. Cutting edge: TLR4 deficiency confers susceptibility to lethal oxidant lung injury. J. Immunol., 175(8):4834–4838.
Zhang, Y., Chen, H., Yang, L., 2010. Toll-like receptor 4 participates in gastric mucosal protection through Cox-2 and PGE2. Dig. Liver Dis., 42(7):472–476. [doi:10.1016/j.dld.2009.10.007]
Zheng, L., Riehl, T.E., Stenson, W.F., 2009. Regulation of colonic epithelial repair in mice by Toll-like receptors and hyaluronic acid. Gastroenterology, 137(6):2041–2051. [doi:10.1053/j.gastro.2009.08.055]
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Project (No. C140404) supported by National Natural Science Foundation of China
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Chen, H., Mahaseth, M. & Zhang, Y. 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 12, 712–719 (2011). https://doi.org/10.1631/jzus.B1000362
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DOI: https://doi.org/10.1631/jzus.B1000362