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PMID: 16085694 Published · ppublish English Journal Article

Monocyte chemoattractant protein 1 and macrophage cyclooxygenase 2 expression in colonic adenoma.

Gut ·Vol. 55 ·No. 1 ·2006-01-00 ·Pages 54-61

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

Abstract

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. 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) E(2) and vascular endothelial growth factor (VEGF) release, were examined in human macrophages isolated from peripheral blood. 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)-1alpha and MIP-1beta, 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 PGE(2) and VEGF release in human macrophages. Celecoxib, a selective COX-2 inhibitor, inhibited MCP-1-induced PGE(2) and VEGF release in macrophages. Addition of exogenous PGE(2) 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. 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.

MeSH Terms
Adenoma/metabolism Adult Aged Aged, 80 and over Antigens, CD/analysis Antigens, Differentiation, Myelomonocytic/analysis Celecoxib Cells, Cultured Chemokine CCL2/antagonists & inhibitors,metabolism,pharmacology Chemokines/metabolism Colorectal Neoplasms/metabolism Cyclooxygenase 1/metabolism Cyclooxygenase 2/metabolism Cyclooxygenase Inhibitors/pharmacology Dinoprostone/metabolism,pharmacology Enzyme-Linked Immunosorbent Assay/methods Female Humans Macrophages/drug effects,enzymology Male Middle Aged Neoplasm Proteins/metabolism Pyrazoles/pharmacology Sulfonamides/pharmacology Tissue Culture Techniques Vascular Endothelial Growth Factor A/metabolism
Chemicals
Antigens, CD Antigens, Differentiation, Myelomonocytic CD68 antigen, human Chemokine CCL2 Chemokines Cyclooxygenase Inhibitors Neoplasm Proteins Pyrazoles Sulfonamides Vascular Endothelial Growth Factor A Cyclooxygenase 1 Cyclooxygenase 2 Celecoxib Dinoprostone
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Tanaka S
Third Department of Internal Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
Tatsuguchi A
Futagami S
Gudis K
Wada K
Seo T
Mitsui K
Yonezawa M
Nagata K
Fujimori S
Tsukui T
Kishida T
Sakamoto C
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Article Info
Journal
Gut
Abbr.
Gut
ISSN
0017-5749
DOI
10.1136/gut.2004.059824
Published
2006-01-00
Epub
2005-00-05
Pages
54-61
Language
English
Region
England
NLM ID
2985108R
PMCID
PMC1856393
Subset
IM
External Links
PubMed source DOI: 10.1136/gut.2004.059824 PMC Full Text View journal details
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