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This Article Full Text Full Text (PDF) All Versions of this Article: 291/2/L244    most recent 00474.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Fayon, M. Articles by Marthan, R. Search for Related Content PubMed PubMed Citation Articles by Fayon, M. Articles by Marthan, R.

Increased secretion of leukemia inhibitory factor by immature airway smooth muscle cells enhances intracellular signaling and airway contractility

¹Laboratoire de Physiologie Cellulaire Respiratoire, Université Victor Segalen Bordeaux 2, and Institut National de la Santé et de la Recherche Médicale, E-356, Bordeaux; ²Centre Hospitalier Universitaire de Bordeaux, Hôpital Pédiatrique, Unité de Pneumologie Pédiatrique et Centre de Recherche, Bordeaux; ³Service d'Immunologie and ⁴Service de Chirurgie Pédiatrique Bordeaux; and ⁵Centre Hospitalier Universitaire de Clermont Ferrand, Service de Pneumologie et Reanimation Pédiatrique F. Clermond, Ferrand, France

Submitted 9 November 2005 ; accepted in final form 10 February 2006

Airway smooth muscle cells (ASMC) play a major role in airway inflammation, hyperresponsiveness, and obstruction in asthma. However, very little is known regarding the relation between inflammatory mediators and cytokines and immature ASMC. The aim of this study was to evaluate 1) the secretion of leukemia inhibitory factor (LIF) (an IL-6 family neurotrophic cytokine) by ASMC; 2) intracellular calcium concentration ([Ca²⁺]_i) signaling; and 3) the effect of LIF on mast cell chemotaxis and rat airway contractility. Immature and adult human ASMC were cultured. ELISA and real-time PCR were performed to assess LIF protein secretion and mRNA production, [methyl-³H]thymidine incorporation to quantify ASMC DNA synthesis, a Boyden chamber to evaluate the effect of LIF on mast cell chemotaxis, microspectroflurimetry using indo-1 (at baseline and after stimulation bradykinin, U-46619, histamine, and acetylcholine, in the presence or absence of LIF or TNF-) for [Ca²⁺]_i signaling, and isolated rat pup tracheae to determine the effect of LIF on airway contractility to ACh. TNF--stimulated immature ASMC produce more LIF mRNA and protein than adult ASMC, although this cytokine induces a moderate increase in DNA synthesis (+20%) in adult ASMC only. Human recombinant LIF exerts no chemotactic effect on human mast cells. In immature ASMC, ACh-induced [Ca²⁺]_i response was enhanced twofold after incubation with LIF, whereas TNF- increased the [Ca²⁺]_i to U-46619 threefold. In TNF--exposed adult ASMC, [Ca²⁺]_i responses to ACh were of greater magnitude (sixfold increase) than in immature ASMC. Human recombinant LIF increased contractility to ACh by 50% in immature, isolated rat tracheae. Stimulated immature human ASMC greatly secrete LIF, thus potentially contributing to neuroimmune airway inflammation and subsequent remodeling. Increased LIF secretion enhances airway reactivity and [Ca²⁺]_i signaling.

calcium signaling; bronchial hyperreactivity; asthma