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Tumour necrosis factor‐α activates a calcium sensitization pathway in guinea‐pig bronchial smooth muscle
Author(s) -
Parris James R. M.,
Cobban Hannah J.,
Littlejohn Alison F.,
MacEwan David J.,
Nixon Graeme F.
Publication year - 1999
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1999.0561p.x
Subject(s) - myofilament , myosin light chain kinase , medicine , endocrinology , tumor necrosis factor alpha , intracellular , myosin , sensitization , calmodulin , calcium in biology , phosphorylation , muscle contraction , calcium , biology , myocyte , microbiology and biotechnology , chemistry , immunology
1 The effects of tumour necrosis factor‐α (TNF) on guinea‐pig bronchial smooth muscle contractility were investigated. 2 The Ca 2+ ‐activated contractile response of permeabilized bronchial smooth muscle strips was significantly increased after incubation with 1 μg ml −1 TNF for 45 min. This TNF‐induced effect was not due to a further increase in intracellular Ca 2+ . 3 The TNF‐induced Ca 2+ sensitization was, at least partly, the result of an increase in myosin light chain 20 phosphorylation. 4 The intracellular signalling pathway involved in this effect of TNF was further investigated. Sphingomyelinase, a potential mediator of TNF, had no effect on Ca 2+ sensitivity of permeabilized bronchial smooth muscle. Also, p42/p44 mitogen‐activated protein kinase (p42/p44 mapk ), activated by TNF in some cell types, did not show an increased activation in bronchial smooth muscle after TNF treatment. 5 In conclusion, TNF may activate a novel signalling pathway in guinea‐pig bronchial smooth muscle leading to an increase in myosin light chain 20 phosphorylation and a subsequent increase in Ca 2+ sensitivity of the myofilaments. This pathway does not appear to involve sphingomyelinase‐liberated ceramides or activation of p42/p44 mapk . Given the importance of TNF in asthma, this TNF‐induced Ca 2+ sensitization of the myofilaments may represent a mechanism responsible for airway hyper‐responsiveness.