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Crucial pathophysiological role of CXCR2 in experimental ulcerative colitis in mice
Author(s) -
Buanne Pasquale,
Di Carlo Emma,
Caputi Lorenzo,
Brandolini Laura,
Mosca Marco,
Cattani Franca,
Pellegrini Luigi,
Biordi Leda,
Coletti Gino,
Sorrentino Carlo,
Fedele Guido,
Colotta Francesco,
Melillo Gabriella,
Bertini Riccardo
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0207118
Subject(s) - cxc chemokine receptors , colitis , ulcerative colitis , pathophysiology , infiltration (hvac) , immunology , biology , chemokine , inflammatory bowel disease , inflammation , pathology , medicine , chemokine receptor , disease , endocrinology , physics , thermodynamics
Polymorphonuclear leukocyte infiltration and activation into colonic mucosa are believed to play a pivotal role in mediating tissue damage in human ulcerative colitis (UC). Ligands of human CXC chemokine receptor 1 and 2 (CXCR1/R2) are chemoattractants of PMN, and high levels were found in the mucosa of UC patients. To investigate the pathophysiological role played by CXCR2 in experimental UC, we induced chronic experimental colitis in WT and CXCR2 −/− mice by two consecutive cycles of 4% dextran sulfate sodium administration in drinking water. In wild‐type (WT) mice, the chronic relapsing of DSS‐induced colitis was characterized by clinical signs and histopathological findings that closely resemble human disease. CXCR2 −/− mice failed to show PMN infiltration into the mucosa and, consistently with a key role of PMN in mediating tissue damage in UC, showed limited signs of mucosal damage and reduced clinical symptoms. Our data demonstrate that CXCR2 plays a key pathophysiological role in experimental UC, suggesting that CXCR2 activation may represent a relevant pharmacological target for the design of novel pharmacological treatments in human UC.