Pulmonary and Activation-Regulated Chemokine Stimulates Collagen Production in Lung Fibroblasts

Sergei P. Atamas, Irina G. Luzina, Jung Choi, Natalya Tsymbalyuk, Nicholas H. Carbonetti, Ishwar S. Singh, Maria Trojanowska, Sergio A. Jimenez, Barbara White

Research output: Contribution to journalArticle

Abstract

Levels of pulmonary and activation-regulated chemokine (PARC) mRNA and protein are increased in the lungs of patients with pulmonary fibrosis. The purpose of this study was to establish whether PARC could be directly involved in development of pulmonary fibrosis by stimulating collagen production in lung fibroblasts. Exposure to PARC increased production of collagen mRNA and protein by 3- to 4-fold In normal adult lung and dermal fibroblast cells. Collagen mRNA transiently increased after 3-6 h of activation with PARC, with an increase in collagen protein detected after 24 h of activation. At the same time, PARC had less pronounced effect on fibroblast proliferation, not exceeding 50% increase over control nonstimulated cells. PARC intracellular signaling led to activation of ERK1/2, but not p38, in fibroblasts; pharmacologic inhibition of ERK, but not p38, also blocked PARC's effect on collagen production. Inhibition experiments with pertussis toxin suggested that PARC receptor is G protein-coupled. Thus, PARC is a member of the CC chemokine family that acts directly as a profibrotic factor.

Original languageEnglish (US)
Pages (from-to)743-749
Number of pages7
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume29
Issue number6
DOIs
StatePublished - Dec 2003
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology

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    Atamas, S. P., Luzina, I. G., Choi, J., Tsymbalyuk, N., Carbonetti, N. H., Singh, I. S., Trojanowska, M., Jimenez, S. A., & White, B. (2003). Pulmonary and Activation-Regulated Chemokine Stimulates Collagen Production in Lung Fibroblasts. American Journal of Respiratory Cell and Molecular Biology, 29(6), 743-749. https://doi.org/10.1165/rcmb.2003-0078OC