The proposed research is an extension of ongoing studies of airway smooth muscle (ASM) cell development and function. The broad goals are to define mechanisms which regulate expression of functionally critical genes, including m c receptors, pp junctions, and smooth muscle actin, and to elucidate the process governing ASM cell proliferation. Specifically, cultured human airway smooth (HASM) cells will be used to define: a. The role of inflammatory cells and, more specifically, the cytokines 11 -beta, and TNF in regulating HASM cells proliferation, gene expression, and, ultimately contractility. b. The role of the autonomic nervous system in the regulation of HASM cell proliferation and phenotypic expression. Specifically, interactions between cultured HASM and cultured autonomic neurons will be examined in depth. c. Second messenger systems which mediate effects of innervation and of cytokines on HASM cell function. The long term goal of these studies is to define mechanisms underlying airway hyperreactivity in diseases such as asthma and COPD. It is hoped that these studies will indicate biochemical and molecular loci where therapeutic intervention will help to ameliorate such bronchopulmonary disorders.
