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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Okazaki, T. Articles by Okumura, K. Search for Related Content PubMed PubMed Citation Articles by Okazaki, T. Articles by Okumura, K. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB BLEOMYCIN Medline Plus Health Information Pulmonary Fibrosis

Impairment of Bleomycin-Induced Lung Fibrosis in CD28-Deficient Mice¹

Tatsuma Okazaki^*, Atsuhito Nakao, Hiroyasu Nakano^*,, Fumiyuki Takahashi, Kazuhisa Takahashi, Osamu Shimozato^*, Kazuyoshi Takeda^*,, Hideo Yagita^*, and Ko Okumura^2,*,

Departments of ^* Immunology, Respiratory Medicine, and Atopy (Allergy) Research Center, Juntendo University School of Medicine, Tokyo, Japan; and Core Research for Evolutional Science and Technology, Japan Science and Technology Cooperation, Tokyo, Japan

Lung fibrosis is an important pulmonary disease with a high mortality rate, but its pathophysiological mechanism has not been fully clarified. Various types of cells have been implicated in the development of lung fibrosis, including T cells. However, the contribution of functional molecules expressed on T cells to the development of lung fibrosis remains largely unknown. In this study, we determined whether costimulation via CD28 on T cells was crucial for the development of lung fibrosis by intratracheally administering bleomycin into CD28-deficient mice. Compared with wild-type mice, the CD28-deficient mice showed markedly impaired lung fibrosis after injection with low doses of bleomycin, as judged by histological changes and hydroxyproline content in the lungs. In addition, bleomycin-induced T cell infiltration into the airways and production of several cytokines and chemokines including IL-5 were also impaired in the CD28-deficient mice. Furthermore, adoptive transfer of CD28-positive T cells from wild-type mice recovered the impaired bleomycin-induced lung fibrosis in CD28-deficient mice. These findings suggest that the CD28-mediated T cell costimulation plays a critical role in the development of lung fibrosis, possibly by regulating the production of cytokines and chemokines in the lung. Thus, manipulation of the CD28-mediated costimulation could be a potential therapeutic strategy for the prevention of lung fibrosis.

This article has been cited by other articles:

				I. G. Luzina, N. W. Todd, A. T. Iacono, and S. P. Atamas Roles of T lymphocytes in pulmonary fibrosis J. Leukoc. Biol., February 1, 2008; 83(2): 237 - 244. [Abstract] [Full Text] [PDF]

				K. Pochetuhen, I. G. Luzina, V. Lockatell, J. Choi, N. W. Todd, and S. P. Atamas Complex Regulation of Pulmonary Inflammation and Fibrosis by CCL18 Am. J. Pathol., August 1, 2007; 171(2): 428 - 437. [Abstract] [Full Text] [PDF]

				J. H. Kim, H. Y. Kim, S. Kim, J.-H. Chung, W. S. Park, and D. H. Chung Natural Killer T (NKT) Cells Attenuate Bleomycin-Induced Pulmonary Fibrosis by Producing Interferon-{gamma} Am. J. Pathol., November 1, 2005; 167(5): 1231 - 1241. [Abstract] [Full Text] [PDF]

				K. Singbartl, S. G.{b.}e Bockhorn, A. Zarbock, M. Schmolke, and H. Van Aken T Cells Modulate Neutrophil-Dependent Acute Renal Failure during Endotoxemia: Critical Role for CD28 J. Am. Soc. Nephrol., March 1, 2005; 16(3): 720 - 728. [Abstract] [Full Text] [PDF]

				S. Sato, M. Fujimoto, M. Hasegawa, K. Komura, K. Yanaba, I. Hayakawa, T. Matsushita, and K. Takehara Serum soluble CTLA-4 levels are increased in diffuse cutaneous systemic sclerosis Rheumatology, October 1, 2004; 43(10): 1261 - 1266. [Abstract] [Full Text] [PDF]

				C. Stambe, R. C. Atkins, G. H. Tesch, T. Masaki, G. F. Schreiner, and D. J. Nikolic-Paterson The Role of p38{alpha} Mitogen-Activated Protein Kinase Activation in Renal Fibrosis J. Am. Soc. Nephrol., February 1, 2004; 15(2): 370 - 379. [Abstract] [Full Text] [PDF]