Inflammatory Mediators in Airway Muscle Proliferation

Abstract

Chronic severe asthma is characterized by airway smooth muscle hypertrophy-hyperplasia that may be intricately related to chronic airway hyperreactivity. We conducted studies to examine the mitogenic effects of inflammatory mediators on airway smooth muscle in reference to known growth factors of smooth muscle. Potential therapeutic agents for airway smooth muscle proliferation were tested in bovine tracheal myocyte tissue culture system. β-Hexosaminidase B (50 nM) caused an increase in 3H-thymidine incorporation in confluent cells comparable to the effect of the optimum concentration of insulin (5 μM) and tumor necrosis factor alpha (6 nM). The mitogenic effect of Hex B was superior in magnitude to that of the optimum concentration of histamine (100 μM), platelet-derived growth factor (0.14 nM), insulinlike growth factor-II (10 nM), and transforming growth factor alpha 14 (nM). Hex B-induced mitogenic effect was significantly inhibited by disodium cromoglycate (DSCG, 10-20 mM) but not by either cyclooxygenase inhibitor indomethacin (10 μM) or 5-lipoxygenase inhibitor AA861 (1 μM). We conclude that inflammatory mediators implicated in asthma (Hex B, histamine) contribute to airway smooth muscle proliferation. The results of this study also suggest that DSCG has a novel antimitogenic function in airway smooth muscle.