Activation of tumor necrosis factor receptor 1 in airway smooth muscle: a potential pathway that modulates bronchial hyper-responsiveness in asthma?

Respir Res. 2000;1(1):49-53. doi: 10.1186/rr12. Epub 2000 Jul 3.


The cellular and molecular mechanisms that are involved in airway hyper-responsiveness are unclear. Current studies suggest that tumor necrosis factor (TNF)-alpha, a cytokine that is produced in considerable quantities in asthmatic airways, may potentially be involved in the development of bronchial hyper-responsiveness by directly altering the contractile properties of the airway smooth muscle (ASM). The underlying mechanisms are not known, but growing evidence now suggests that most of the biologic effects of TNF-alpha on ASM are mediated by the p55 receptor or tumor necrosis factor receptor (TNFR)1. In addition, activation of TNFR1 coupled to the tumor necrosis factor receptor-associated factor (TRAF)2-nuclear factor-kappaB (NF-kappaB) pathway alters calcium homeostasis in ASM, which appears to be a new potential mechanism underlying ASM hyper-responsiveness.

Publication types

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

MeSH terms

  • Animals
  • Asthma / physiopathology*
  • Bronchi / physiopathology*
  • Bronchial Hyperreactivity / physiopathology*
  • Humans
  • Muscle, Smooth / physiopathology*
  • Protein Isoforms / physiology
  • Receptors, Tumor Necrosis Factor / physiology*


  • Protein Isoforms
  • Receptors, Tumor Necrosis Factor