Monocyte-chemoattractant protein 1 gene expression in intestinal epithelial cells and inflammatory bowel disease mucosa.
BACKGROUND
Monocyte-chemoattractant protein 1 (MCP-1) activates macrophages and increases the migration of monocytes into tissue during inflammation. It was hypothesized that MCP-1 expression is involved in intestinal inflammation.


METHODS
MCP-1 protein was detected by immunohistochemistry and immunoprecipitation. Biological activity of MCP-1 was assessed using a chemotactic assay. MCP-1 messenger RNA (mRNA) levels were measured by quantitative reverse-transcription polymerase chain reaction.


RESULTS
In normal mucosa, MCP-1 was predominantly present in surface epithelium. In contrast, inflamed mucosa from patients with ulcerative colitis or Crohn's disease contained multiple cells immunoreactive for MCP-1, including spindle cells, mononuclear cells, and endothelial cells. Furthermore, MCP-1 mRNA expression was markedly increased in inflamed intestinal biopsy specimens from patients with inflammatory bowel disease. MCP-1 was detected in isolated intestinal epithelial cells and in conditioned media from Caco-2 cells. Caco-2 cell-conditioned media stimulated monocyte chemotaxis activity that was inhibited by anti-MCP-1 antibodies. Constituitive MCP-1 mRNA levels in Caco-2 cells were up-regulated by interleukin 1 beta and down-regulated by dexamethasone.


CONCLUSIONS
In addition to lamina propria macrophages, endothelial cells, and spindle cells, intestinal epithelial cells are able to produce MCP-1. MCP-1 is expressed constitutively in the intestinal colonic mucosa and is up-regulated during inflammation.
Reinecker
H C
HC
Division of Gastroenterology, University of Pennsylvania Medical Center, Philadelphia.
Loh
E Y
EY
Ringler
D J
DJ
Mehta
A
A
Rombeau
J L
JL
MacDermott
R P
RP
D001483:Base Sequence; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000235:genetics* / Q000378:metabolism; D003106:Colon / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004751:Enteritis / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000473:pathology; D007375:Interleukin-1 / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000473:pathology / Q000503:physiopathology*; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D018932:Chemokine CCL2; D002630:Chemotactic Factors; D016207:Cytokines; D007375:Interleukin-1; D015335:Molecular Probes; D012333:RNA, Messenger; D013755:Tetradecanoylphorbol Acetate