IN-VITRO PROCOLLAGEN SYNTHESIS AND PROLIFERATIVE PHENOTYPE OF BRONCHIAL FIBROBLASTS FROM NORMAL AND ASTHMATIC SUBJECTS

Asthma is characterized histologically by a bronchial subepithelial fi brosis. Cytokines and other mediators released in the asthmatic chroni c inflammatory microenvironment can activate the repair process that l eads to fibroblast proliferation and collagen synthesis. To our knowle dge, there are no data regarding the effect of a chronic inflammatory microenvironment on the phenotype of human bronchial fibroblasts. In t he present study, we address this issue by comparing bronchial fibrobl asts isolated from normal and asthmatic subjects in terms of: (a) prol iferation over cell passage; (b) in vitro lifespan; (c) proliferative response to transforming growth factor-beta 1, platelet-derived growth factor-BB, dexamethasone, and retinoic acid; and (d) base-line synthe sis of procollagens I and III. Bronchial fibroblasts from asthmatic su bjects demonstrated lower DNA synthesis with cell passage than bronchi al fibroblasts from normals. The in vitro lifespan of asthmatic bronch ial fibroblasts was lower than in those from normal subjects and was s ignificantly correlated with airway responsiveness. Platelet-derived g rowth factor-BB and dexamethasone increased H-3-thymidine incorporatio n in asthmatic bronchial fibroblasts without having any significant ef fect on normal fibroblast proliferation. Transforming growth factor-be ta 1 and retinoic acid had no significant effect on bronchial fibrobla st proliferation. Base-line procollagens I and III synthesis measureme nts showed no differences between normal and asthmatic fibroblasts. Ta ken together, these results indicate that the chronic inflammatory mic roenvironment found in asthma can modulate some aspects of bronchial f ibroblast phenotype.