Collagen-binding integrin alpha1beta1 regulates intestinal inflammation in experimental colitis. Export

@article{citeulike:6029180, abstract = {Central to inflammatory responses are the integrin-mediated adhesive interactions of cells with their ECM-rich environment. We investigated the role of the collagen-binding integrin alpha(1)beta(1) in intestinal inflammation using the mouse model of colitis induced by dextran sodium sulfate (DSS). mAb's directed against murine alpha(1) were found to significantly attenuate inflammation and injury in DSS-treated wild-type mice; similar protection was seen in mice deficient for alpha(1)beta(1) integrin. Blockade or loss of alpha(1)beta(1) was also associated with decreased mucosal inflammatory cell infiltrate and cytokine production. Importantly, we demonstrated that development and alpha(1)-mediated inhibition of DSS-induced colitis occurred independently of lymphocytes (Rag-2(-/-) mice), and identified the monocyte as a key alpha(1)beta(1)-expressing cell type involved in the development of colitis in this model. In response to DSS, both alpha(1) deficiency and anti-alpha(1) mAb treatment significantly reduced monocyte accumulation and activation within the lamina propria. In summary, the data demonstrate that engagement of leukocyte-associated alpha(1)beta(1) receptors with ECM plays a pivotal role in mediating intestinal inflammation via promotion of monocyte movement and/or activation within the inflamed interstitium. Therapeutic strategies designed to disrupt such interactions may prove beneficial in treating intestinal inflammation.}, author = {Krieglstein, Christian F. and Cerwinka, Wolfgang H. and Sprague, Andrew G. and Laroux, F. Stephen and Grisham, Matthew B. and Koteliansky, Victor E. and Senninger, Norbert and Granger, D. Neil and de Fougerolles, Antonin R.}, citeulike-article-id = {6029180}, citeulike-linkout-0 = {http://dx.doi.org/10.1172/JCI15256}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/12488427}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=12488427}, doi = {10.1172/JCI15256}, issn = {0021-9738}, journal = {The Journal of clinical investigation}, keywords = {colitis, collagen, vla-1}, month = {December}, number = {12}, pages = {1773--1782}, posted-at = {2009-10-28 22:02:56}, priority = {2}, title = {Collagen-binding integrin alpha1beta1 regulates intestinal inflammation in experimental colitis.}, url = {http://dx.doi.org/10.1172/JCI15256}, volume = {110}, year = {2002} }

TY - JOUR ID - citeulike:6029180 L3 - citeulike-article-id:6029180 N2 - Central to inflammatory responses are the integrin-mediated adhesive interactions of cells with their ECM-rich environment. We investigated the role of the collagen-binding integrin alpha(1)beta(1) in intestinal inflammation using the mouse model of colitis induced by dextran sodium sulfate (DSS). mAb's directed against murine alpha(1) were found to significantly attenuate inflammation and injury in DSS-treated wild-type mice; similar protection was seen in mice deficient for alpha(1)beta(1) integrin. Blockade or loss of alpha(1)beta(1) was also associated with decreased mucosal inflammatory cell infiltrate and cytokine production. Importantly, we demonstrated that development and alpha(1)-mediated inhibition of DSS-induced colitis occurred independently of lymphocytes (Rag-2(-/-) mice), and identified the monocyte as a key alpha(1)beta(1)-expressing cell type involved in the development of colitis in this model. In response to DSS, both alpha(1) deficiency and anti-alpha(1) mAb treatment significantly reduced monocyte accumulation and activation within the lamina propria. In summary, the data demonstrate that engagement of leukocyte-associated alpha(1)beta(1) receptors with ECM plays a pivotal role in mediating intestinal inflammation via promotion of monocyte movement and/or activation within the inflamed interstitium. Therapeutic strategies designed to disrupt such interactions may prove beneficial in treating intestinal inflammation. IS - 12 JF - The Journal of clinical investigation SN - 0021-9738 EP - 1782 TI - Collagen-binding integrin alpha1beta1 regulates intestinal inflammation in experimental colitis. VL - 110 SP - 1773 KW - colitis KW - collagen KW - vla-1 AU - Krieglstein, Christian AU - Cerwinka, Wolfgang AU - Sprague, Andrew AU - Laroux, Stephen AU - Grisham, Matthew AU - Koteliansky, Victor AU - Senninger, Norbert AU - Granger, Neil AU - de Fougerolles, Antonin PY - 2002/12// UR - http://dx.doi.org/10.1172/JCI15256 ER -