Helper T cell type 1 and 2 cytokines regulate C-C chemokine expression in mouse pleural mesothelial cells

Am J Respir Crit Care Med. 1999 May;159(5 Pt 1):1653-9. doi: 10.1164/ajrccm.159.5.9810011.

Abstract

The recruitment of leukocytes to an area of injury or inflammation site is one of the most fundamental host defenses. Pulmonary tuberculosis is characterized by granulomatous inflammation with an extensive infiltration of mononuclear cells. In tuberculous pleurisy pleural mesothelial cells are exposed to mycobacteria in the pleural space. In this study we demonstrate that mouse pleural mesothelial cells (PMCs), when stimulated with BCG or IFN-gamma, produced MIP-1alpha and MCP-1 in vitro. IFN-gamma enhanced the BCG-mediated MIP-1alpha and MCP-1 expression in a concentration-dependent manner. The RT-PCR studies also confirmed that both BCG and IFN-gamma induce chemokine expression. IL-4 inhibited the BCG-mediated MIP-1alpha and MCP-1 expression in a concentration-dependent manner. The lower concentrations of IL-4 were ineffective; however, at higher concentrations, the inhibitory effect of IL-4 persisted for 24 h and decreased thereafter. BCG stimulation resulted in an increase of IFN-gamma and IL-4 receptors on PMCs. Our results demonstrate that Th1 and Th2 cytokines may regulate the C-C chemokine expression in PMCs and thus play a biologically important role in mononuclear cell recruitment to the pleural space.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism*
  • Chemokine CCL3
  • Chemokine CCL4
  • Cytokines / metabolism
  • Cytokines / physiology*
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Female
  • Interferon-gamma / metabolism
  • Interferon-gamma / pharmacology
  • Interleukin-4 / pharmacology
  • Macrophage Inflammatory Proteins / genetics
  • Macrophage Inflammatory Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium bovis / physiology
  • Pleura / cytology
  • Pleura / drug effects
  • Pleura / metabolism*
  • RNA, Messenger / metabolism
  • Receptors, Interleukin-4 / metabolism
  • T-Lymphocytes, Helper-Inducer / metabolism*

Substances

  • Chemokine CCL2
  • Chemokine CCL3
  • Chemokine CCL4
  • Cytokines
  • Macrophage Inflammatory Proteins
  • RNA, Messenger
  • Receptors, Interleukin-4
  • Interleukin-4
  • Interferon-gamma