Carbon monoxide suppresses bleomycin-induced lung fibrosis. Academic Article uri icon

Overview

MeSH

  • Animals
  • Cell Cycle
  • Cell Division
  • Cyclic AMP
  • Cyclic GMP
  • Hydroxyproline
  • Male
  • Mice
  • Mice, Inbred CBA

MeSH Major

  • Bleomycin
  • Carbon Monoxide
  • Pulmonary Fibrosis

abstract

  • Idiopathic pulmonary fibrosis is an incurable fibrosing disorder that progresses relentlessly to respiratory failure. We hypothesized that a product of heme oxygenase activity, carbon monoxide (CO), may have anti-fibrotic effects. To test this hypothesis, mice treated with intratracheal bleomycin were exposed to low-concentration inhaled CO or ambient air. Lungs of mice treated with CO had significantly lower hydroxyproline accumulation than controls. Fibroblast proliferation, thought to play a central role in the progression of fibrosis, was suppressed by in vitro exposure to CO. CO caused increased cellular levels of p21(Cip1) and decreased levels of cyclins A and D. This effect was independent of the observed suppression of MAPK's phosphorylation by CO but was dependent on increased cGMP levels. Further, CO-exposed cells elaborated significantly less fibronectin and collagen-1 than control cells. This same effect was seen in vivo. Suppression of collagen-1 production did not depend on MAPK or guanylate cyclase signaling pathways but did depend on the transcriptional regulator Id1. Taken together, these data suggest that CO exerts an anti-fibrotic effect in the lung, and this effect may be due to suppression of fibroblast proliferation and/or suppression of matrix deposition by fibroblasts.

publication date

  • January 2005

has subject area

  • Animals
  • Bleomycin
  • Carbon Monoxide
  • Cell Cycle
  • Cell Division
  • Cyclic AMP
  • Cyclic GMP
  • Hydroxyproline
  • Male
  • Mice
  • Mice, Inbred CBA
  • Pulmonary Fibrosis

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC1602308

Digital Object Identifier (DOI)

  • 10.1016/S0002-9440(10)62229-8

PubMed ID

  • 15631997

Additional Document Info

start page

  • 27

end page

  • 37

volume

  • 166

number

  • 1