A novel role for constitutively expressed epithelial-derived chemokines as antibacterial peptides in the intestinal mucosa.
Intestinal-derived chemokines have a central role in orchestrating immune cell influx into the normal and inflamed intestine. Here, we identify the chemokine CCL6 as one of the most abundant chemokines constitutively expressed by both murine small intestinal and colonic epithelial cells. CCL6 protein localized to crypt epithelial cells, was detected in the gut lumen and reached high concentrations at the mucosal surface. Its expression was further enhanced in the small intestine following in vivo administration of LPS or after stimulation of the small intestinal epithelial cell line, mIC(c12), with IFNgamma, IL-4 or TNFalpha. Recombinant- and intestinal-derived CCL6 bound to a subset of the intestinal microflora and displayed antibacterial activity. Finally, the human homologs to CCL6, CCL14 and CCL15 were also constitutively expressed at high levels in human intestinal epithelium, were further enhanced in inflammatory bowel disease and displayed similar antibacterial activity. These findings identify a novel role for constitutively expressed, epithelial-derived chemokines as antimicrobial peptides in the intestinal mucosa.
Kotarsky
K
K
Immunology Section, Department of Experimental Medical Sciences, Lund University, Lund, Sweden. Knut.Kotarsky@med.lu.se
Sitnik
K M
KM
Stenstad
H
H
Kotarsky
H
H
Schmidtchen
A
A
Koslowski
M
M
Wehkamp
J
J
Agace
W W
WW
D000818:Animals; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001422:Bacterial Adhesion / Q000187:drug effects / Q000276:immunology; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000235:genetics; D016207:Cytokines / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D019073:HT29 Cells; D006801:Humans; D007114:Immunization; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D007413:Intestinal Mucosa / Q000473:pathology; D008070:Lipopolysaccharides / Q000008:administration & dosage; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL
D000900:Anti-Bacterial Agents; C097720:CCL14 protein, human; C108814:CCL15 protein, human; D019742:Chemokines, CC; D016207:Cytokines; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; C070959:Ccl6 protein, mouse