Histamine stimulates proliferation of airway smooth muscle and induces c-fos expression. Academic Article uri icon

Overview

abstract

  • Although chronic severe asthma is characterized by increased smooth muscle mass in the airways, the physiological stimuli that promote airway smooth muscle (ASM) proliferation (hyperplasia) or increase ASM protein expression (hypertrophy) are unknown. We examined the effects of histamine, an autocoid associated with airway hyperresponsiveness, on protein synthesis, myosin heavy chain expression, and cell proliferation in cultured canine ASM cells. In confluent ASM cells, histamine significantly increased incorporation of [35S]-methionine in protein. Maintenance of the proportion of smooth muscle-specific myosin heavy chain to total myosin heavy chain suggested a nonspecific increase in contractile protein expression. DNA synthesis, as measured by [3H]thymidine incorporation, was significantly increased by histamine in a concentration-dependent manner. Cell proliferation paralleled [3H]thymidine incorporation; histamine significantly increased cell numbers at 24 and 48 h of stimulation. Because growth of mesenchymal-derived cells is associated with transcription of c-fos mRNA, we examined whether histamine altered expression of this proto-oncogene. Histamine-treated cells showed marked increases in expressions of steady-state c-fos mRNA, with a time course of mRNA induction similar to cells exposed to platelet-derived growth factor or serum, known smooth muscle and fibroblast cell mitogens. Therefore, histamine is an ASM mitogen with an action similar to other mesenchymal cell growth factors and may play a role in the hyperplasia of ASM in asthma.

publication date

  • December 1, 1990

Research

keywords

  • DNA Replication
  • Histamine
  • Muscle, Smooth
  • Proto-Oncogene Proteins
  • Proto-Oncogenes
  • Trachea

Identity

Scopus Document Identifier

  • 0025667854

Digital Object Identifier (DOI)

  • 10.1152/ajplung.1990.259.6.L365

PubMed ID

  • 2124421

Additional Document Info

volume

  • 259

issue

  • 6 Pt 1