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- Title
Expression and effects of cardiotrophin-1 (CT-1) in human airway smooth muscle cells.
- Authors
Danyi Zhou, Michaela; Xueyan Zheng, Michaela; Lu Wang; Stelmack, Gerald; Halayko, Andrew J.; Dorscheid, Delbert; Bai, Tony R.
- Abstract
1 Cellular hypertrophy and/or a reduced rate of apoptosis could increase airway smooth muscle mass. As cardiotrophin-1 (CT-1) induces hypertrophy and inhibits apoptosis in cardiomyocytes, we tested for the expression and effects of' CT-I in human bronchial smooth muscle cells (HBSMC). 2 CT-1 was detected in abundance in normal adult human lung and was expressed in both fetal and adult HBSMC. 3 Following serum deprivation, CT-1 was released by reintroduction of serum and by TGF- β2/ IL-4 in fetal but not adult cells. TGF-β 2/ IL-4 triggered the release of CT-1 in serum-fed adult cells. Hypoxia and strain had no effect on the release of CT-1. 4 CT-l reduced the apoptosis induced both by serum deprovation and by Fas antibody TNF-α treatment in adult cells, with greater efficacy than other members of the IL-6 superfamily. The MAPK/ERK kinase inhibitor PD98059 (1 - 10μM0 I reduced the effect of CT-1. Fetal cells were more resistant to apopiosis. 5 CT-1 (10 ng ml[sup-1]) induced a significant increase in cell size as judged by protein/DNA ratios and flow cytometry. No effects on smooth muscle α-actin or vimentin proteins were noted, although CT-1 qualitatively alters the cytoslructural distribution of SM22 an actin filament-associated protein, and increased SM22 prolcin abundance. No effect on proliferation or migration was evident. 6 These data suggest CT-1 expression primarily in fetal and synthetic HBSMC phenotypes. By reducing the rates of apopiosis and inducing hypertrophy, CT-1 may contribute to increased smooth muscle mass in airway disease.
- Subjects
ASTHMA; CYTOMETRY; SMOOTH muscle; INTERLEUKIN-6; APOPTOSIS; HYPERTROPHY; THERAPEUTICS
- Publication
British Journal of Pharmacology, 2003, Vol 140, Issue 7, p1237
- ISSN
0007-1188
- Publication type
Article
- DOI
10.1038/sj.bjp.0705562