Chest ACCP Education Calendar
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Guest Access | Sign In via User Name/Password
This Article
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ortiz, L. A.
Right arrow Articles by Friedman, M.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Ortiz, L. A.
Right arrow Articles by Friedman, M.
(Chest. 2001;120:S2-S3.)
© 2001 American College of Chest Physicians

Tumor Necrosis Factor Receptor Deficiency Protects Mice From Silica-Induced Lung Fibrosis by Altering Lung Matrix Metalloproteinase-13/Tissue Inhibitor of Metalloproteinase-1 RNA Expression and Decreasing Activating Protein-1 Activation*

Luis A. Ortiz, MD, FCCP; Joseph A. Lasky, MD, FCCP; Evelyn Gozal, PhD; Arnold R. Brody, PhD; Annie Pardo, PhD; Moises Selman, MD, FCCP; Victor Ruiz, MD and Mitchell Friedman, MD, FCCP

* From the Department of Medicine (Drs. Ortiz, Lasky, Gazal, Brody, and Friedman), Tulane Medical Center, New Orleans, LA; and Instituto de Enfermedades Respiratorias (Drs. Pardo, Selman, and Ruiz), Mexico City, Mexico.

Correspondence to: Luis A. Ortiz, MD, FCCP, Department of Medicine, Section of Pulmonary Diseases, Critical Care and Environmental Medicine SL9, 1430 Tulane Ave, New Orleans, LA 70112-2699

Murine exposure to silica is associated with enhanced tumor necrosis factor (TNF) expression and upregulation of genes responsible for matrix deposition (collagen, matrix metalloproteinases [MMPs], and their inhibitors). The regulation of TNF is mediated through TNF receptor (TNFR)-dependent activation of nuclear transcription factors. We have previously shown that double TNFR-deficient mice (55-/75-) are resistant to silica-induced pulmonary fibrosis.1 We now have studied the effect of TNFR deletion upon RNA expression of interstitial collagenase (MMP-13) and its inhibitor (tissue inhibitor of metalloproteinase [TIMP]-1) in the lungs of silica-treated mice. We correlated the MMP-13/TIMP-1 RNA expression with the activation of the nuclear transcription factors activating protein (AP)-1 and nuclear factor (NF)-{kappa}B in the lungs of C57BL/6, and single [(55-/- or 75-/-)] TNFR-deficient mice exposed to silica (0.2 g/kg) or saline solution by intratracheal instillation. Animals were killed 28 days after exposure, and lung hydroxyproline, MMP-13, and TIMP-1 RNA expression and AP-1 and NF-{kappa}B activation were measured using standard methods. Mice that were p55 -/- or p 75 -/- deficient had significantly decreased lung hydroxyproline accumulation (p < 0.05). Significantly enhanced MMP-13 RNA expression was observed in all murine strains, but enhanced TIMP-1 RNA expression was observed only in C57BL/6 mice in response to silica exposure. NF-{kappa}B activation was observed in all strains, while AP-1 activation was seen only in C57BL/6 mice after silica exposure. These data suggest that (1) TNFR deletion modifies MMP-13/TIMP-1 expression in favor of matrix degradation, and (2) decreased AP-1 activation explains the suppressed TIMP-1 expression in TNFR-deficient mice.

Footnotes

Abbreviations: AP = activating protein; MMP = matrix metalloproteinase; NF = nuclear factor; TIMP = tissue inhibitor of metalloproteinase; TNF = tumor necrosis factor; TNFR = tumor necrosis factor receptor

References

  1. Ortiz, LA, Lasky, J, Lungarella, G, et al (1999) Upregulation of the p75 but not the p55 TNF-{alpha} receptor mRNA after silica and bleomycin exposure and protection from lung injury in double receptor knockout mice. Am J Respir Cell Mol Biol 20,825-833[Abstract/Free Full Text]




This Article
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ortiz, L. A.
Right arrow Articles by Friedman, M.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Ortiz, L. A.
Right arrow Articles by Friedman, M.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS