MAPK pathway mediates EGR-1-HSP70-dependent cigarette smoke-induced chemokine production

Chao Jun Li, Wen Ning, Michael A. Matthay, Carol A. Feghali-Bostwick, Augustine M.K. Choi

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

Cigarette smoking, a major risk factor for chronic obstructive pulmonary disease, can cause airway inflammation, airway narrowing, and loss of elasticity, leading to chronic airflow limitation. In this report, we sought to define the signaling pathways activated by smoke and to identify molecules responsible for cigarette smoke-induced inflammation. We applied cigarette smoke water extract (CSE) to primary human lung fibroblasts and found that CSE significantly increased CXC chemokine IL-8 production. Meanwhile, 70-kDa heat shock protein (HSP70) was also induced by CSE in a dose- and time-dependent manner. CSE treatment stimulated HSP70 secretion by primary fibroblasts, which augmented IL-8 production. This was further confirmed by exogenously added recombinant HSP70. Using HSP70 small interfering RNA, we confirmed that CSE-induced chemokine production was dependent on heat shock protein expression. Further investigation showed that CSE could also stimulate early growth response-1 (EGR-1) in an ERK-dependent manner and that the expression of HSP70 was EGR-1 dependent. In view of these findings, we hypothesize that the MAPK-EGR-1-HSP70 pathway regulates the cigarette smoke-induced inflammatory process.

Original languageEnglish (US)
Pages (from-to)L1297-L1303
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume292
Issue number5
DOIs
StatePublished - May 2007

Keywords

  • 70-kDa heat shock protein
  • Chronic obstructive pulmonary disease
  • Cigarette smoke extract
  • Early growth response-1
  • Interleukin-8

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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