Contribution of PKC to beta-hexosaminidase-induced airway smooth muscle proliferation

beta-Hexosaminidases (Hex) A and B promote mitogenesis via airway smooth muscle (ASM) mannose receptor. The objective of this study was to elucidate the contribution of protein kinase C (PKC) in Hex-induced mitogenesis in ASM cells (ASMC). Exposure of ASMC to Hex caused increases in both the calcium-dependent and the calcium-independent PKC activities. Both downregulation of PKC and PKC inhibitors staurosporine and calphostin C diminished Hex-induced DNA synthesis and cell number. Hex-induced DNA synthesis was enhanced by a diacylglycerol kinase inhibitor, R-59022, which was blocked by calphostin C. These data suggest that activation of PKC in part mediates Hex-induced mitogenesis in ASMC.