PMID: 7544535Aug 1, 1995Paper

Leukotriene D4 facilitates airway smooth muscle cell proliferation via modulation of the IGF axis

The American Journal of Physiology
P CohenM M Grunstein

Abstract

The insulin-like growth factor (IGF) axis is involved in regulating proliferation in a variety of cell types, including airway smooth muscle. Because airway hyperplasia is a characteristic feature of asthma and other lung diseases, we examined the interaction of the potent proinflammatory eicosanoid leukotriene D4 (LTD4) with the IGF axis in regulating airway smooth muscle cell mitogenesis. In cultured rabbit airway smooth muscle cells, IGF-I but not LTD4 was mitogenic at submaximal concentrations. The combination of the two agents exerted a significant synergistic effect on airway smooth muscle cell mitogenesis. Analysis of airway smooth muscle cell conditioned medium by Western ligand blotting demonstrated a marked LTD4-induced reduction in the levels of the predominant IGF binding protein IGFBP-2, which is elaborated into the conditioned medium. The latter effect on IGFBP-2 release was not associated with a reduction in IGFBP-2 mRNA levels; however, LTD4-treated airway smooth muscle conditioned medium demonstrated the presence of a lower molecular weight form of IGFBP-2 by cross-linking to IGFs and specific proteolysis of radiolabeled IGFBP-2. IGFBP-2 was also noted to be associated with airway smooth muscle cell membranes, ...Continue Reading

Citations

Oct 15, 2008·Annual Review of Physiology·Omar Tliba, Reynold A Panettieri
Jul 19, 2018·BioMed Research International·Zheng WangXiaoju Zhang
Nov 17, 1998·American Journal of Respiratory and Critical Care Medicine·R A Panettieri
Sep 2, 2008·American Journal of Physiology. Lung Cellular and Molecular Physiology·Rodolfo P VieiraCelso R F Carvalho
Oct 31, 2002·American Journal of Respiratory and Critical Care Medicine·Richard LeighPaul M O'Byrne
Jul 21, 2007·American Journal of Respiratory Cell and Molecular Biology·Rodolfo P VieiraMarisa Dolhnikoff
Apr 9, 2018·The Journal of Allergy and Clinical Immunology·Ubong PetersErick Forno
Jan 28, 2021·American Journal of Physiology. Lung Cellular and Molecular Physiology·Becky J ProskocilZhenying Nie

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