Y Masunaga1, T Noto, K Suzuki, K Takahashi, Y Shimizu, T Morokata. 1. Department of Immunology, Pharmacology Research Laboratories, Institute for Drug Discovery Research, Astellas Pharma Inc., 1-6, Kashima 2-Chome, Yodogawa-ku, Osaka, 532-8514, Japan.
Abstract
OBJECTIVE: MDR1a-/- mice spontaneously develop colitis as the result of imperfect epithelial barrier derived from MDR1a deficiency in the large intestine; however, the pathogenesis is not well understood. This study investigated the expression profiles of cytokines and chemokines in murine MDR1a-/- colitis. METHODS: MDR1a-/- and wild-type FVB mice were monitored from the 6th to the 16th week of age. Production of various cytokines and chemokines in the large intestine and mesenteric lymph node (MLN) cells was examined. RESULTS: Inflammatory cell infiltration, IL-1beta production, and MPO activity were aberrantly enhanced in the tissue of MDR1a-/- mice. Under various stimuli, MLN cells produced higher levels of Th1-type (IFN-gamma, IL-2, and IL-12) and proinflammatory (IL-1beta and TNF-alpha) cytokines. Inflammatory chemokines MIP-2/CXCL2, KC/CXCL1, MIP-1alpha/CCL3, MCP-1/CCL2, and RANTES/CCL5 were also markedly upregulated in the tissue. CONCLUSION: Since the expression profiles of cytokines and chemokines correspond well with those in human IBD, MDR1a-/- mouse is a useful model for the analysis of IBD pathophysiology.
OBJECTIVE:MDR1a-/- mice spontaneously develop colitis as the result of imperfect epithelial barrier derived from MDR1a deficiency in the large intestine; however, the pathogenesis is not well understood. This study investigated the expression profiles of cytokines and chemokines in murineMDR1a-/- colitis. METHODS:MDR1a-/- and wild-type FVB mice were monitored from the 6th to the 16th week of age. Production of various cytokines and chemokines in the large intestine and mesenteric lymph node (MLN) cells was examined. RESULTS: Inflammatory cell infiltration, IL-1beta production, and MPO activity were aberrantly enhanced in the tissue of MDR1a-/- mice. Under various stimuli, MLN cells produced higher levels of Th1-type (IFN-gamma, IL-2, and IL-12) and proinflammatory (IL-1beta and TNF-alpha) cytokines. Inflammatory chemokines MIP-2/CXCL2, KC/CXCL1, MIP-1alpha/CCL3, MCP-1/CCL2, and RANTES/CCL5 were also markedly upregulated in the tissue. CONCLUSION: Since the expression profiles of cytokines and chemokines correspond well with those in human IBD, MDR1a-/- mouse is a useful model for the analysis of IBD pathophysiology.
Authors: Kelley Mk Haarberg; Meghan J Wymore Brand; Anne-Marie C Overstreet; Catherine C Hauck; Patricia A Murphy; Jesse M Hostetter; Amanda E Ramer-Tait; Michael J Wannemuehler Journal: World J Gastrointest Pharmacol Ther Date: 2015-11-06