Monocyte chemoattractant protein 1 and macrophage cyclooxygenase 2 expression in colonic adenoma. Issue 1 (5th August 2005)

• Record Type: Journal Article
• Authors: Tanaka, S; Tatsuguchi, A; Futagami, S; Gudis, K; Wada, K; Seo, T; Mitsui, K; Yonezawa, M; Nagata, K; Fujimori, S; Tsukui, T; Kishida, T; Sakamoto, C
• Is Part Of: Gut. Volume 55:Issue 1(2006)
• Page Start: 54
• Page End: 61
• Publication Date: 2005-08-05
• Subjects: COX-2, cyclooxygenase 2 -- MCP-1, macrophage chemoattractant protein -- PG, prostaglandin -- VEGF, vascular endothelial growth factor -- RANTES, regulated on activation of normal T cell expressed and secreted -- ELISA, enzyme linked immunosorbent assay -- MIP, macrophage inflammatory protein -- NSAIDs, non-steroidal anti-inflammatory drugs -- FAP, familial adenomatous polyposis -- H&E, haematoxylin and eosin -- PBS, phosphate buffered saline -- EDTA, ethylenediaminetetraacetic acid -- PMSF, phenylmethylsulfonyl fluoride -- FITC, fluorescein isothiocyanate -- PBMC, peripheral blood mononuclear cells -- FCS, fetal calf serum -- LPS, lipopolysaccharide -- CHAPS, 3-[(3, cholamidopropyl)-dimethylammonio]-l-propane-sulfonate; cyclooxygenase -- macrophage chemoattractant protein -- adenoma -- macrophage; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gut.2004.059824
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : Background and aims: Cyclooxygenase 2 (COX-2) expression in subepithelial macrophages of colorectal adenoma has been suggested as the first in a series of steps leading to colorectal tumorigenesis. We tested the hypothesis that chemokines released from human colorectal adenoma epithelium might be involved in COX-2 expression in macrophages of the lamina propria. Methods: Endoscopic samples of sporadic colorectal adenomas were tested by enzyme linked immunosorbent assay for chemokines involved in macrophage chemotaxis. Localisation of adenoma macrophage chemoattractant protein 1 (MCP-1) and COX-2 were determined by immunohistochemistry. The effects of MCP-1, in the presence or absence of celecoxib, on COX-2 expression, and prostaglandin (PG) E2 and vascular endothelial growth factor (VEGF) release, were examined in human macrophages isolated from peripheral blood. Results: MCP-1 levels were markedly higher in adenoma with mild-moderate dysplasia (129.7 (19.9) pg/mg protein) and severe dysplasia (227.9 (35.4) pg/mg protein) than in normal colonic mucosa (55.8 (4.2) pg/mg protein). Other chemokine levels, macrophage inflammatory proteins (MIP)-1α and MIP-1β, and the chemokine regulated on activation of normal T cell expressed and secreted (RANTES) did not vary significantly between adenoma and normal mucosa. MCP-1 levels in both adenoma and normal colonic mucosa increased significantly three hours after tissue cultivation in vitro. MCP-1 immunoreactivity was restricted to the adenoma epithelium, with no reactivity seen in adjacent normal epithelial cells. MCP-1 stimulated COX-2 expression and PGE2 and VEGF release in human macrophages. Celecoxib, a selective COX-2 inhibitor, inhibited MCP-1-induced PGE2 and VEGF release in macrophages. Addition of exogenous PGE2 reversed this inhibitory effect on VEGF release, suggesting that MCP-1 in adenoma epithelial cells might be involved in COX-2 expression and subsequent macrophage activation. Conclusions: MCP-1 in colorectal adenoma epithelial cells might be involved in macrophage migration and COX-2 expression, leading to the subsequent development of colonic adenoma.