Differential and regulated expression of C-X-C, C-C, and C-chemokines by human colon epithelial cells.
OBJECTIVE
Intestinal epithelial cells constitute a barrier between host and external milieu and can play a role in signaling the influx of leukocytes during the acute mucosal inflammatory response. To further explore this role, the regulated expression of twelve C-X-C, C-C, and C-chemokines by human colon epithelial cells was characterized.


METHODS
Chemokine production was assessed in HT-29 and Caco-2 human colon epithelial cells that were infected with Salmonella dublin or stimulated with interleukin 1 alpha or tumor necrosis factor alpha and in freshly isolated human colon epithelial cells by quantitative reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay.


RESULTS
Expression of the neutrophil chemoattractants GRO-alpha, GRO-gamma, and interleukin 8 increased rapidly (2-3 hours) but transiently after infection or proinflammatory agonist stimulator. In contrast, expression of another neutrophil chemoattractant, epithelial cell-derived neutrophil activator 78, was delayed for 6-10 hours, and secretion continued to increase for 24 hours after infection. Among C-C chemokines known to chemoattract different leukocyte populations, monocyte chemotactic peptide 1 was rapidly expressed, whereas RANTES was up-regulated with delayed kinetics. Freshly isolated colon epithelial cells produced an array of chemokines similar to the cell lines, as well as macrophage inflammatory proteins 1 alpha and 1 beta.


CONCLUSIONS
These data suggest that regulated chemokine production by epithelial cells results in temporal and spatial mucosal chemokine gradients that are important in both early and later phases of the mucosal inflammatory response.
Yang
S K
SK
Department of Medicine, University of California at San Diego, La Jolla, USA.
Eckmann
L
L
Panja
A
A
Kagnoff
M F
MF
D000230:Adenocarcinoma; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054360:Chemokine CXCL1; D018925:Chemokines / Q000096:biosynthesis*; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000096:biosynthesis; D003106:Colon; D003110:Colonic Neoplasms; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006133:Growth Substances / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D007700:Kinetics; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000494:pharmacology; D012475:Salmonella; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
C475829:CXCL1 protein, human; C499707:CXCL3 protein, human; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D017931:DNA Primers; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha