Background: The increase in ASMC mass is a major structural change described in asthma. This increase has been attributed to ASMC hyperplasia and hypertrophy. Recent studies have suggested a role of chemokines in SMC migration toward the epithelium. The objective of the current study is to test the hypothesis that chemokines (Eotaxin, RANTES, IL-8 and MIP-1α) can increase the rate of proliferation and enhance the survival of ASM cells. Methods: ASMCs were exposed to different concentrations of eotaxin, RANTES, IL-8 or MIP-1α. To test for proliferation, stimulated ASMC were pulsed with 3H-thymidine or ASMCs were stained with BrdU and then analyzed with flow cytometry. Apoptosis was measured using Annexin-V and flow cytometry. Results: In a concentration-dependent manner, chemokines such as Eotaxin, RANTES, IL-8 and MIP-1α increased ASMCs 3H-thymidine incorporation and DNA synthesis. This increase, however, was inhibited using ERK1/2 phosphorylation inhibitors. IL-8, Eotaxin, and MIP-1α decreased the number of apoptotic ASMCs compared to the matched controls. Conclusion: We conclude that chemokines might contribute to airway remodeling seen in asthma by increasing ASM mass through enhancing ASMCs proliferation and survival. | | | |