|
|
||||||||
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Higashiku, Fukuoka 812-8582, Japan
We previously demonstrated essential
roles of the Fas-Fas ligand (FasL) pathway in bleomycin-induced
pneumopathy in mice. T lymphocytes and natural killer cells express
FasL on activation and use it as a cytotoxic effector molecule. Because
interleukin (IL)-12 is known to play a critical role in cell-mediated
immunity, we investigated whether anti-IL-12 antibody treatment
suppresses the development of this model. The anti-IL-12 antibody
treatment decreased the number of apoptotic cells and the degree of
inflammation and fibrosis in lung tissue. The results of RT-PCR showed
that IL-12p40, IL-12 receptor (R)
2, interferon-
, tumor necrosis factor-
and FasL mRNAs were upregulated after bleomycin
instillation. The upregulation of FasL, IL-12R
2, and tumor necrosis
factor-
mRNA expression in lung tissue was suppressed by anti-IL-12
antibody treatment. The results of enzyme-linked immunosorbent assay
showed that the levels of IL-12p40, but not of IL-12p70, were increased in lung tissue after bleomycin instillation. Although the increase in
IL-12R
2 mRNA levels suggests that the T helper type 1 cell response
may participate in lung injury, the increase in IL-12p40 supports T
helper type 2 cell predominance in the fibrotic process of this model.
The administration of anti-IL-12 antibody could be a novel therapy
against lung injury and pulmonary fibrosis.
T helper type 1 cell; T helper type 2 cell; Fas-Fas ligand pathway; apoptosis
This article has been cited by other articles:
![]() |
T. R. McMillan, B. B. Moore, J. B. Weinberg, K. M. Vannella, W. B. Fields, P. J. Christensen, L. F. van Dyk, and G. B. Toews Exacerbation of Established Pulmonary Fibrosis in a Murine Model by Gammaherpesvirus Am. J. Respir. Crit. Care Med., April 1, 2008; 177(7): 771 - 780. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Yamada, K. Kuwano, T. Maeyama, M. Yoshimi, N. Hamada, J. Fukumoto, K. Egashira, K. Hiasa, K. Takayama, and Y. Nakanishi Gene transfer of soluble transforming growth factor type II receptor by in vivo electroporation attenuates lung injury and fibrosis J. Clin. Pathol., August 1, 2007; 60(8): 916 - 920. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. R. Young, R. Pasula, P. M. Gulleman, G. H. Deutsch, and F. X. McCormack Susceptibility of Hermansky-Pudlak Mice to Bleomycin-Induced Type II Cell Apoptosis and Fibrosis Am. J. Respir. Cell Mol. Biol., July 1, 2007; 37(1): 67 - 74. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Inoshima, K. Kuwano, N. Hamada, N. Hagimoto, M. Yoshimi, T. Maeyama, A. Takeshita, S. Kitamoto, K. Egashira, and N. Hara Anti-monocyte chemoattractant protein-1 gene therapy attenuates pulmonary fibrosis in mice Am J Physiol Lung Cell Mol Physiol, May 1, 2004; 286(5): L1038 - L1044. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Inoshima, K. Kuwano, N. Hamada, M. Yoshimi, T. Maeyama, N. Hagimoto, Y. Nakanishi, and N. Hara Induction of CDK inhibitor p21 gene as a new therapeutic strategy against pulmonary fibrosis Am J Physiol Lung Cell Mol Physiol, April 1, 2004; 286(4): L727 - L733. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. J. Segel, G. Izbicki, P. Y. Cohen, R. Or, T. G. Christensen, S. B. Wallach-Dayan, and R. Breuer Role of interferon-{gamma} in the evolution of murine bleomycin lung fibrosis Am J Physiol Lung Cell Mol Physiol, December 1, 2003; 285(6): L1255 - L1262. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Huaux, T. Liu, B. McGarry, M. Ullenbruch, and S. H. Phan Dual Roles of IL-4 in Lung Injury and Fibrosis J. Immunol., February 15, 2003; 170(4): 2083 - 2092. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Huaux, M. Arras, D. Tomasi, V. Barbarin, M. Delos, J.-P. Coutelier, A. Vink, S. H. Phan, J.-C. Renauld, and D. Lison A Profibrotic Function of IL-12p40 in Experimental Pulmonary Fibrosis J. Immunol., September 1, 2002; 169(5): 2653 - 2661. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |