Dextran sulfate sodium-induced inflammation is enhanced by intestinal epithelial cell chemokine expression in mice.
Dextran sulfate sodium (DSS) induces an inflammatory bowel disease-like colitis in animals. To determine the contribution of epithelium to inflammation in the intestine, we examined the effects of DSS in transgenic mice that specifically secrete macrophage inflammatory protein-2 (MIP-2) from the intestinal epithelium. We first confirmed the production of MIP-2 from intestinal epithelial cells by Western blots in transgenic mice. MIP-2 transgenic mice were therefore an appropriate model to examine the role of epithelial cell chemokines in an inflammatory state induced by DSS. We then examined the neutrophil migration into the intestine and the effect of DSS on this migration by myeloperoxidase staining. There was an increase of myeloperoxidase-positive neutrophils in the intestine from wild-type and transgenic mice after the DSS treatment. Furthermore, the increase of neutrophils under stimulation with DSS was confirmed quantitatively by measuring specific tissue myeloperoxidase activities. It was significantly greater in DSS-treated MIP-2 transgenic mice than in wild-type mice in both the small intestine and colon. These results suggest that the inflammatory effects of DSS on both small intestine and colon are enhanced by MIP-2 secreted by epithelial cells in the transgenic mice. In conclusion, intestinal epithelial cells can act in concert with other inflammatory stimuli in maintaining inflammation.
Ohtsuka
Yoshikazu
Y
Department of Adult and Paediatric Gastroenterology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, London, U.K.
Sanderson
Ian R
IR
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D054426:Chemokine CXCL2; D019743:Chemokines, CXC; D016264:Dextran Sulfate / Q000494:pharmacology*; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D007249:Inflammation / Q000139:chemically induced*; D036341:Intercellular Signaling Peptides and Proteins; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D015846:Monokines / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins
C499706:CXCL2 protein, human; D002352:Carrier Proteins; D054426:Chemokine CXCL2; D019743:Chemokines, CXC; C082667:Fabp5 protein, mouse; C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D015846:Monokines; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D016264:Dextran Sulfate