Monocyte chemoattractant protein-1 production by intestinal epithelial cells in vitro: a role for p38 in epithelial chemokine expression.
The intestinal epithelial cell (IEC) represents the first cellular barrier to infection. Consistent with this sentinel role, IEC are known to produce a variety of chemokines in response to bacterial infection or proinflammatory cytokines. These chemokines act as potent leukocyte activators and chemoattractants in vivo. In this report, we begin to characterize the regulation of expression of the chemokine monocyte chemoattractant protein-1 (MCP-1) in the rat small intestinal IEC-18 line. Following stimulation with either interleukin-1beta (IL-1beta) or lipopolysaccharide (LPS), IEC-18 cells produced MCP-1, with IL-1 proving a more effective stimulus than LPS at both the mRNA and protein levels. Expression of MCP-1 due to either stimulus was inhibited by tyrosine kinase inhibitors, prompting us to investigate potential phosphotyrosine-dependent targets responsible for MCP-1 expression. We detected activation of p38, a member of the mitogen-activated protein kinase family, following either IL-1 or LPS treatment. Specific inhibition of this kinase using the compound SB203580 caused a destabilization of MCP-1 mRNA. These data point to a role for p38 in the regulation of MCP-1 mRNA expression by the IEC.
Waterhouse
C C
CC
Department of Microbiology and Immunology, Dalhousie University, Halifax, NS Canada.
Joseph
R R
RR
Winsor
G L
GL
Lacombe
T A
TA
Stadnyk
A W
AW
D000818:Animals; D002460:Cell Line; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D018925:Chemokines / Q000096:biosynthesis*; D015536:Down-Regulation / Q000276:immunology; D004789:Enzyme Activation / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000494:pharmacology; D020871:RNA Stability / Q000276:immunology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases
D018932:Chemokine CCL2; D018925:Chemokines; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases