| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
American Journal of Pathology, Vol 152, 513-522, Copyright © 1998 by American Society for Investigative Pathology
REGULAR ARTICLES |
EW Uhl, LL Moldawer, WW Busse, TJ Jack and WL Castleman
Department of Pathobiology, University of Florida, Gainesville 32610- 0145, USA.
Increased airway resistance and airway hyperresponsiveness induced in rats by infection with parainfluenza type I (Sendai) virus is associated with bronchiolar fibrosis. To determine whether increased tumor necrosis factor (TNF)-alpha gene expression is an important regulatory event in virus-induced bronchiolar fibrosis, pulmonary TNF- alpha mRNA and protein expression was assessed in rat strains that are susceptible (Brown Norway; BN) and resistant (Fischer 344; F344) to virus-induced bronchiolar fibrosis. Virus-inoculated BN rats had increased TNF-alpha pulmonary mRNA levels (P < 0.05) and increased numbers of bronchiolar macrophages and fibroblasts expressing TNF-alpha protein compared with virus-inoculated F344 rats (P < 0.05). Virus inoculation also induced elevated TNF-alpha mRNA and protein levels (P < 0.05) in cultured rat alveolar macrophages (NR8383 cells). A 55-kd soluble TNF receptor-immunoglobulin G fusion protein (sTNFR-IgG) was used to inhibit TNF-alpha bioactivity in virus-inoculated BN rats. Treated rats had fewer proliferating bronchiolar fibroblasts, as detected by bromodeoxyuridine incorporation, compared with virus- inoculated control rats (P < 0.05). There was also increased mortality in p55sTNFR-IgG-treated virus-inoculated rats associated with increased viral replication and decreased numbers of macrophages and lymphocytes in bronchoalveolar lavage fluid (P < 0.05). The results of this study indicate that 1) Sendai virus can directly up-regulate TNF-alpha mRNA and protein expression in macrophages, 2) TNF-alpha is an important mediator of virus-induced bronchiolar fibrosis, and 3) TNF-alpha has a critical role in the termination of Sendai viral replication in the lung.
This article has been cited by other articles:
![]() |
X. Cai and W. L. Castleman Early high expression of IP-10 in F344 rats resistant to Sendai virus-induced airway injury Am J Physiol Lung Cell Mol Physiol, December 1, 2003; 285(6): L1263 - L1269. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Lin, A. C. Bright, T. A. Rothermel, and B. He Induction of Apoptosis by Paramyxovirus Simian Virus 5 Lacking a Small Hydrophobic Gene J. Virol., March 15, 2003; 77(6): 3371 - 3383. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. R. Meusel, K. E. Kehoe, and F. Imani Protein Kinase R Regulates Double-Stranded RNA Induction of TNF-{alpha} But Not IL-1{beta} mRNA in Human Epithelial Cells J. Immunol., June 15, 2002; 168(12): 6429 - 6435. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Smith and S. Letendre Viral Pneumonia as a Serious Complication of Etanercept Therapy Ann Intern Med, January 15, 2002; 136(2): 174 - 174. [Full Text] [PDF] |
||||
![]() |
H. Zhang, C. Snead, and J. D. Catravas Nitric Oxide Differentially Regulates Induction of Type II Nitric Oxide Synthase in Rat Vascular Smooth Muscle Cells Versus Macrophages Arterioscler. Thromb. Vasc. Biol., April 1, 2001; 21(4): 529 - 535. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. L. SORKNESS, W. L. CASTLEMAN, A. KUMAR, M. R. KAPLAN, and R. F. LEMANSKE Jr. Prevention of Chronic Postbronchiolitis Airway Sequelae with IFN-gamma Treatment in Rats Am. J. Respir. Crit. Care Med., August 1, 1999; 160(2): 705 - 710. [Abstract] [Full Text] |
||||
![]() |
J.-Y. Liu, D. M. Brass, G. W. Hoyle, and A. R. Brody TNF-{alpha} Receptor Knockout Mice Are Protected from the Fibroproliferative Effects of Inhaled Asbestos Fibers Am. J. Pathol., December 1, 1998; 153(6): 1839 - 1847. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |