HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Song, X.-y. Articles by Wahl, S. M. Search for Related Content PubMed PubMed Citation Articles by Song, X.-y. Articles by Wahl, S. M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Liver Diseases

Inhibition of Bacterial Cell Wall-Induced Leukocyte Recruitment and Hepatic Granuloma Formation by TGF-ß Gene Transfer

Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892

Intraperitoneal injection of streptococcal cell walls (SCW) into Lewis rats results in dissemination of SCW to the liver, spleen, bone marrow, and peripheral joints. The uptake of SCW by Kupffer cells in the liver initiates a chain of events largely mediated by T lymphocytes and macrophages. Local synthesis and secretion of cytokines and growth factors in response to the persistent SCW lead to the evolution and maintenance of a chronic T cell-dependent granulomatous response and result in granuloma formation and irreversible hepatic fibrosis. In an attempt to impede the development of the chronic granulomatous lesions in the liver, we injected a plasmid DNA encoding TGF-ß1 i.m. to the SCW animals to determine the effect of TGF-ß1 gene transfer on the course of liver inflammation and fibrosis. A single injection of plasmid DNA encoding TGF-ß1 resulted in virtual abolition of the development of the SCW-induced hepatic granuloma formation and matrix expansion. TGF-ß1 DNA not only reduced key proinflammatory cytokines including TNF-, IL-1ß, IFN-, and IL-18, but also inhibited both CXC and CC chemokine production, thereby blocking inflammatory cell recruitment and accumulation in the liver. Moreover, TGF-ß1 gene delivery inhibited its own expression in the liver tissue, which is otherwise up-regulated in SCW-injected animals. Our study suggests that TGF-ß1 gene transfer suppresses hepatic granuloma formation by blocking the recruitment of inflammatory cells to the liver, and thus may provide a new approach to the control of hepatic granulomatous and fibrotic diseases.

This article has been cited by other articles:

				H. S. Oz, M. Ray, T. S. Chen, and C. J. McClain Efficacy of a Transforming Growth Factor {beta}2 Containing Nutritional Support Formula in a Murine Model of Inflammatory Bowel Disease J. Am. Coll. Nutr., June 1, 2004; 23(3): 220 - 226. [Abstract] [Full Text] [PDF]

				D. Haller, L. Holt, S. C. Kim, R. F. Schwabe, R. B. Sartor, and C. Jobin Transforming Growth Factor-{beta}1 Inhibits Non-pathogenic Gramnegative Bacteria-induced NF-{kappa}B Recruitment to the Interleukin-6 Gene Promoter in Intestinal Epithelial Cells through Modulation of Histone Acetylation J. Biol. Chem., June 20, 2003; 278(26): 23851 - 23860. [Abstract] [Full Text] [PDF]