Expression of the neutrophil chemokine KC in the colon of mice with enterocolitis and by intestinal epithelial cell lines: effects of flora and proinflammatory cytokines.
IL-10 plays an important role in preventing excessive inflammation to the normal flora in the intestinal lumen. The purpose of this study was to compare the effect of normal flora on inflammation in mice in which the IL-10 gene was disrupted. IL-10 knock-out mice housed in germfree conditions remained healthy while those housed in conventional conditions developed colitis after weaning, suggesting that IL-10 inhibits the adverse responses to luminal Ag. Crypt abscesses were present in virtually all of the diseased animals as evidenced by flattening of the epithelial cells and a large number of neutrophils in the lumen of the crypt. Since KC is a chemokine that is capable of recruiting neutrophils in mice, mRNA and protein for KC was measured. Increased levels of both KC mRNA and protein were detected in the colon of diseased mice. To determine whether the epithelial cells were capable of synthesizing KC and contributing to neutrophil accumulation in the crypts, a murine intestinal epithelial cell line (Mode-K) was shown to express mRNA and protein for KC. Two cytokines induced in association with colitis in these mice, TNF-alpha and IFN-gamma, increased the expression of KC mRNA and protein in murine epithelial cells. However, IL-10 was incapable of decreasing the induction of KC, even though the cells expressed the IL-10 receptor. These results suggest that the neutrophil chemokine KC is produced by gastrointestinal epithelial cells in response to inflammatory mediators that are expressed following exposure to normal flora in animals lacking IL-10.
Song
F
F
Department of Pediatrics, University of Texas Medical Branch, Galveston 77555, USA.
Ito
K
K
Denning
T L
TL
Kuninger
D
D
Papaconstantinou
J
J
Gourley
W
W
Klimpel
G
G
Balish
E
E
Hokanson
J
J
Ernst
P B
PB
D000367:Age Factors; D000818:Animals; D002460:Cell Line; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics; D002630:Chemotactic Factors / Q000096:biosynthesis* / Q000235:genetics; D003106:Colon / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D016207:Cytokines / Q000502:physiology*; D004760:Enterocolitis / Q000276:immunology / Q000382:microbiology* / Q000401:mortality / Q000473:pathology; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D006133:Growth Substances / Q000096:biosynthesis* / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012737:Sex Factors