Interaction of vimentin and phosphorylated mitogen-activated protein kinases in FcϵRI and CC chemokine receptor 1 engaged mast cells (44.18)

Abstract

Abstract Accumulating evidence points to cross-talk between FcϵRI and CC chemokine receptor (CCR)-mediated signaling pathways in mast cells. Here, we propose that vimentin, a protein composing type III intermediate filament, participates in such cross-talk for CCL2/ monocyte chemotactic protein 1 production in mast cells. Co-stimulation via FcϵRI, with IgE/antigen, and CCR1, with recombinant CCL3/macrophage inflammatory protein-1α increased expression of phosphorylated, disassembled and soluble vimentin in rat basophilic leukemia (RBL)-2H3 cells expressing human CCR1 (RBL-CCR1 cells), a model of mucosal type mast cells. Furthermore, the co-stimulation enhanced production of CCL2 and phosphorylation of mitogen-activated protein (MAP) kinases. Treating the cells with p38 MAP kinase inhibitor SB203580, but not with MAP kinase kinase (MEK) inhibitor PD98058, reduced CCL2 production, suggesting that p38 MAP kinase, but not extracellular-signal-regulated kinase 1/2 (ERK1/2), plays a critical role in the chemokine production. Immunoprecipitation analysis showed association of vimentin with phosphorylated ERK1/2 and p38 MAP kinases in the co-simulated cells. Preventing formation of the soluble vimentin by aggregating vimentin filaments using beta,beta'-iminodipropionitrile reduced the association of vimentin with phospholylated MAP kinases, and CCL2 production in the cells. Taken together, soluble vimentin could need optimal CCL2 production in mast cells.