Expression of monocyte chemotactic protein (MCP)-1, MCP-2, and MCP-3 by human airway smooth-muscle cells. Modulation by corticosteroids and T-helper 2 cytokines

Am J Respir Cell Mol Biol. 1999 Oct;21(4):528-36. doi: 10.1165/ajrcmb.21.4.3660.

Abstract

We have demonstrated that, in addition to their contractile function, human airway smooth-muscle cells (HASMC) are able to express and to secrete chemokines of the monocyte chemotactic protein (MCP)/ eotaxin subfamily. This group of chemokines is believed to play a fundamental role in the development of allergic airway diseases such as asthma. The expression levels of MCP (MCP-1, -2, and -3) messenger RNA (mRNA) were compared with those of regulated on activation, normal T cells expressed and secreted (RANTES) mRNA in HASMC in culture. HASMC express MCP and RANTES mRNA after stimulation with interleukin (IL)-1beta, tumor necrosis factor-alpha, and interferon-gamma. MCP mRNA was maximal at 8 h, whereas RANTES mRNA expression was delayed to 24 h after stimulation. Further, significant differences were observed in the induction patterns of MCP and RANTES mRNA expression after stimulation with the individual cytokines. Dexamethasone (DEX) significantly inhibited cytokine-induced accumulation of MCP and RANTES mRNA, in contrast to IL-4, IL-10, and IL-13, which had no inhibitory effect on cytokine-induced chemokine expression. The cytokine-induced MCP mRNA expression in HASMC was associated with MCP release, which was inhibited by DEX and post-translationally by IL-4. HASMC can actively participate in the pathogenesis of asthma by the expression and release of chemokines, which are likely to play a critical role in the generation and regulation of the inflammatory response characteristic of allergic airway diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bronchi / cytology
  • Bronchi / drug effects
  • Bronchi / metabolism*
  • Cells, Cultured
  • Chemokine CCL2 / genetics*
  • Chemokine CCL5 / genetics
  • Chemokine CCL7
  • Chemokine CCL8
  • Cycloheximide / pharmacology
  • Cytokines / pharmacology
  • Dexamethasone / pharmacology
  • Gene Expression / drug effects
  • Glucocorticoids / pharmacology
  • Humans
  • Interleukin-10 / pharmacology
  • Interleukin-13 / pharmacology
  • Interleukin-4 / pharmacology
  • Monocyte Chemoattractant Proteins / genetics*
  • Muscle, Smooth / cytology
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Th2 Cells / immunology

Substances

  • CCL7 protein, human
  • CCL8 protein, human
  • Chemokine CCL2
  • Chemokine CCL5
  • Chemokine CCL7
  • Chemokine CCL8
  • Cytokines
  • Glucocorticoids
  • Interleukin-13
  • Monocyte Chemoattractant Proteins
  • RNA, Messenger
  • Interleukin-10
  • Interleukin-4
  • Dexamethasone
  • Cycloheximide