Global gene expression profiles during acute pathogen-induced pulmonary inflammation reveal divergent roles for Th1 and Th2 responses in tissue repair. Export

@article{citeulike:5374336, abstract = {T helper 1 responses are typically proinflammatory, while Th2 responses have been considered regulatory. Interestingly, Th2 responses characterize a number of pulmonary diseases, many of which terminate in tissue remodeling and fibrosis. We developed a mouse model using Schistosoma mansoni eggs and cytokine-deficient mice to induce highly polarized Th1- or Th2-type inflammation in the lung. In this study, we examined the pathology and cytokine profiles in Th1- and Th2-polarized environments and used oligonucleotide microarray analysis to decipher the genes responsible for these effects. We further elaborated on the results using IL-10- and IL-13-deficient mice because these cytokines are believed to be the central regulators of Th2-associated pathology. We found that the Th1-polarized mice developed small granulomas with less fibrosis while expressing genes characteristic of tissue damage. Th2-polarized mice, in contrast, formed large granulomas with massive collagen deposition and up-regulated genes associated with wound healing, specifically, arginase, collagens, matrix metalloproteinases (MMPs), and tissue inhibitors of MMP. In addition, several members of the chitinase-like family were up-regulated in the lung following egg challenge. We also developed a method of defining the net collagen deposition using the expression profiles of several collagen, MMP, and tissue inhibitors of MMP genes. We found that Th1-polarized mice did not elaborate collagens or MMPs and therefore did not have a significant capacity for repair in this model. Thus, Th1-mediated inflammation is characterized by tissue damage, while Th2 directs wound healing and fibrosis.}, author = {Sandler, Netanya G. and Mentink-Kane, Margaret M. and Cheever, Allen W. and Wynn, Thomas A.}, citeulike-article-id = {5374336}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/14500663}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=14500663}, day = {1}, issn = {0022-1767}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, keywords = {gene, inflammation, pathogen-induced, pulmonary, th1, th2, tissue-repair}, month = {October}, number = {7}, pages = {3655--3667}, posted-at = {2009-08-05 20:55:34}, priority = {2}, title = {Global gene expression profiles during acute pathogen-induced pulmonary inflammation reveal divergent roles for Th1 and Th2 responses in tissue repair.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/14500663}, volume = {171}, year = {2003} }

TY - JOUR ID - citeulike:5374336 L3 - citeulike-article-id:5374336 N2 - T helper 1 responses are typically proinflammatory, while Th2 responses have been considered regulatory. Interestingly, Th2 responses characterize a number of pulmonary diseases, many of which terminate in tissue remodeling and fibrosis. We developed a mouse model using Schistosoma mansoni eggs and cytokine-deficient mice to induce highly polarized Th1- or Th2-type inflammation in the lung. In this study, we examined the pathology and cytokine profiles in Th1- and Th2-polarized environments and used oligonucleotide microarray analysis to decipher the genes responsible for these effects. We further elaborated on the results using IL-10- and IL-13-deficient mice because these cytokines are believed to be the central regulators of Th2-associated pathology. We found that the Th1-polarized mice developed small granulomas with less fibrosis while expressing genes characteristic of tissue damage. Th2-polarized mice, in contrast, formed large granulomas with massive collagen deposition and up-regulated genes associated with wound healing, specifically, arginase, collagens, matrix metalloproteinases (MMPs), and tissue inhibitors of MMP. In addition, several members of the chitinase-like family were up-regulated in the lung following egg challenge. We also developed a method of defining the net collagen deposition using the expression profiles of several collagen, MMP, and tissue inhibitors of MMP genes. We found that Th1-polarized mice did not elaborate collagens or MMPs and therefore did not have a significant capacity for repair in this model. Thus, Th1-mediated inflammation is characterized by tissue damage, while Th2 directs wound healing and fibrosis. IS - 7 JF - Journal of immunology (Baltimore, Md. : 1950) SN - 0022-1767 EP - 3667 TI - Global gene expression profiles during acute pathogen-induced pulmonary inflammation reveal divergent roles for Th1 and Th2 responses in tissue repair. VL - 171 SP - 3655 KW - gene KW - inflammation KW - pathogen-induced KW - pulmonary KW - th1 KW - th2 KW - tissue-repair AU - Sandler, Netanya AU - Mentink-Kane, Margaret AU - Cheever, Allen AU - Wynn, Thomas PY - 2003/10/01/ UR - http://view.ncbi.nlm.nih.gov/pubmed/14500663 ER -