MAPK pathway mediates EGR-1-HSP70-dependent cigarette smoke-induced chemokine production. Academic Article uri icon

Overview

MeSH

  • Cell Line
  • Cells, Cultured
  • Fibroblasts
  • Gene Expression Regulation
  • Humans
  • Interleukin-8
  • RNA, Small Interfering

MeSH Major

  • Chemokines
  • DNA, Single-Stranded
  • HSP70 Heat-Shock Proteins
  • Lung
  • Mitogen-Activated Protein Kinases
  • Smoke

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.

publication date

  • May 2007

has subject area

  • Cell Line
  • Cells, Cultured
  • Chemokines
  • DNA, Single-Stranded
  • Fibroblasts
  • Gene Expression Regulation
  • HSP70 Heat-Shock Proteins
  • Humans
  • Interleukin-8
  • Lung
  • Mitogen-Activated Protein Kinases
  • RNA, Small Interfering
  • Smoke

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1152/ajplung.00194.2006

PubMed ID

  • 17494953

Additional Document Info

start page

  • L1297

end page

  • L1303

volume

  • 292

number

  • 5