Table of Contents
Journal of Allergy
Volume 2012, Article ID 783290, 7 pages
http://dx.doi.org/10.1155/2012/783290
Research Article

Calreticulin Is a Negative Regulator of Bronchial Smooth Muscle Cell Proliferation

Departments of Biomedicine, Pulmonary Cell Research, and Thorax Surgery, University Hospital Basel, Hebelstrasse 20, 4031 Basel, Switzerland

Received 26 July 2011; Revised 1 November 2011; Accepted 23 November 2011

Academic Editor: Irene Heijink

Copyright © 2012 Nicola Miglino et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background. Calreticulin controls the C/EBPαp42/p30 at the translational level trough a cis-regulatory CNG rich loop in the CEBPA mRNA. We determined the effects of steroids and long-acting beta-agonists on the p42/p30 ratio and on calreticulin expression in primary human bronchial smooth muscle (BSM) cells. Methods. The effects of budesonide (10−8 M) and formoterol (10−8 M) were studied in BSM cells pre-treated with siRNA targeting calreticulin. The expression of C/EBPα and calreticulin was determined by immuno-blotting. Automated cell counts were performed to measure proliferation. Results. All tested BSM cell lines (n=5) expressed C/EBPα and calreticulin. In the presence of 5% FBS, the p42/p30 ratio significantly decreased (n=3, P<0.05) and coincided with BSM cell proliferation. High levels of calreticulin were associated with a decreased p42/p30 isoform ratio. FBS induced the expression of calreticulin (n=3, P<0.05), which was further increased by formoterol. siRNA targeting calreticulin increased the p42/p30 ratio in non-stimulated BSM cells and significantly inhibited the proliferation of PDGF-BB-stimulated BSM cells (n=5, P<0.05). Neither budesonide nor formoterol restored the p42 isoform expression. Conclusions. Our data show calreticulin is a negative regulator of C/EBPα protein expression in BSM cells. Modulation of calreticulin levels may provide a novel target to reduce BSM remodeling.