Organ culture with proinflammatory cytokines reproduces impairment of the beta-adrenoceptor-mediated relaxation in tracheas of a guinea pig antigen model.

M. Wills-Karp, Y. Uchida, J. Y. Lee, J. Jinot, A. Hirata, F. Hirata

Research output: Contribution to journalArticle

Abstract

The challenge of previously sensitized guinea pigs with aerosolized ovalbumin resulted in impairment of the beta-adrenoceptor-mediated relaxation as measured by the in vitro isometric assay of tracheas preconstricted with endothelin-1 or carbamylcholine. Numbers and affinities of beta-adrenoceptors in lung membranes of these animals were not altered under these conditions, although the antigen challenge caused an inflammatory response, as evident from the accumulation of inflammatory cells in the bronchoalveolar lavage fluids. In order to investigate the pathophysiologic role of inflammation in hyperreactive airways, isolated guinea pig tracheas were cultured with proinflammatory cytokines such as human recombinant tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), or interleukin-2 (IL-2). None of these cytokines affected the contractile response of tracheas to carbamylcholine. After preconstriction with carbamylcholine, the TNF-alpha- and IL-1 beta-pretreated tissues produced a significant reduction in the maximal relaxation induced by isoproterenol, whereas the IL-2 pretreatment had no effect. The reduction of the isoproterenol-mediated relaxation by the IL-1 beta treatment was time and dose dependent. Our present observations suggest that in vitro incubation of naive tracheas with proinflammatory cytokines is able to reproduce apparent beta-adrenoceptor impairment as seen in the airways of antigen-challenged guinea pigs of asthma model.

Original languageEnglish (US)
Pages (from-to)153-159
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Volume8
Issue number2
DOIs
StatePublished - Feb 1993

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'Organ culture with proinflammatory cytokines reproduces impairment of the beta-adrenoceptor-mediated relaxation in tracheas of a guinea pig antigen model.'. Together they form a unique fingerprint.

  • Cite this