Crucial pathophysiological role of CXCR2 in experimental ulcerative colitis in mice

被引:83
作者
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
机构
[1] Dompe pharma spa, Dept Preclin Pharmacol, I-67100 Laquila, Italy
[2] Univ G dAnnunzio, Dept Oncol & Neurosci, Surg Pathol Sect, Chieti, Italy
[3] G Annunzio Univ Fdn, Ce SI Aging Res Ctr, Chieti, Italy
[4] Univ Aquila, Dept Expt Med, I-67100 Laquila, Italy
[5] S Salvatore Reg Hosp, Operat Unit Pathol Anat, Laquila, Italy
[6] Dompe pharma spa, Biometry Unit, Milan, Italy
[7] Nerviano Med Sci, Milan, Italy
关键词
rodent; neutrophils; inflammation;
D O I
10.1189/jlb.0207118
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 I and 2 (CXCR1/R2) are chemoattractants of PAIN, 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 PAIN 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.
引用
收藏
页码:1239 / 1246
页数:8
相关论文
共 45 条
[31]   A NOVEL METHOD IN THE INDUCTION OF RELIABLE EXPERIMENTAL ACUTE AND CHRONIC ULCERATIVE-COLITIS IN MICE [J].
OKAYASU, I ;
HATAKEYAMA, S ;
YAMADA, M ;
OHKUSA, T ;
INAGAKI, Y ;
NAKAYA, R .
GASTROENTEROLOGY, 1990, 98 (03) :694-702
[32]  
PALMEN MJHJ, 1995, CLIN EXP IMMUNOL, V101, P351
[33]   MECHANISMS OF DISEASE Inflammatory Bowel Disease [J].
Abraham, Clara ;
Cho, Judy H. .
NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (21) :2066-2078
[34]   Critical role of endothelial CXCR2 in LPS-induced neutrophil migration into the lung [J].
Reutershan, J ;
Morris, MA ;
Burcin, TL ;
Smith, DF ;
Chang, D ;
Saprito, MS ;
Ley, K .
JOURNAL OF CLINICAL INVESTIGATION, 2006, 116 (03) :695-702
[35]  
Sandborn William J, 2005, Rev Gastroenterol Disord, V5, P10
[36]   HISTOPATHOLOGICAL EVALUATION OF COLONIC MUCOSAL BIOPSY SPECIMENS IN CHRONIC INFLAMMATORY BOWEL-DISEASE - DIAGNOSTIC IMPLICATIONS [J].
SELDENRIJK, CA ;
MORSON, BC ;
MEUWISSEN, SGM ;
SCHIPPER, NW ;
LINDEMAN, J ;
MEIJER, CJLM .
GUT, 1991, 32 (12) :1514-1520
[37]   CXCR2- and E-selectin-induced neutrophil arrest during inflammation in vivo [J].
Smith, ML ;
Olson, TS ;
Ley, K .
JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 200 (07) :935-939
[38]  
Stokes M.E., 1995, CATEGORICAL DATA ANA
[39]  
TALBOT I, 1987, BIOPSY PATHOLOGY COL
[40]   Increased expression of IP-10, IL-8, MCP-1, and MCP-3 in ulcerative colitis [J].
Uguccioni, M ;
Gionchetti, P ;
Robbiani, DF ;
Rizzello, F ;
Peruzzo, S ;
Campieri, M ;
Baggiolini, M .
AMERICAN JOURNAL OF PATHOLOGY, 1999, 155 (02) :331-336