Which receptor(s) is responsible for the mediation of effects of MCP-1 on human tubular epithelial cells?
Chemokines exert their effects through binding to G-protein-coupled receptors on the surface of leukocytes targeted for activation and migration. These receptors, once activated, trigger a set of cellular reactions that result in inositol triphosphate formation, intracellular calcium release, and PKC activation [28]. The classic MCP-1 receptors belong to the family of heptahelical, pertussis-sensitive, G-protein-coupled receptors [29]. The MCP-1 receptor on tubular epithelial cells appears to be coupled to Gi-protein activation [21]. These findings are in accordance with our observations in vascular smooth muscle cells [22], as well as data of others [29,30]. As in leukocytes, MCP-1-induced up-regulation of IL-6 synthesis and ICAM-1 expression by human tubular epithelial cells are dependent on PKC and intracellular Ca2+ (Ca2+i) [21]. Similarly, Schecter et al. [30] demonstrated that the induction of tissue factor by MCP-1 in human vascular smooth muscle cells required Ca2+i mobilizatio