CK beta 8/CCL23 induces cell migration via the Gi/Go protein/PLC/PKC delta/NF-kappa B and is involved in inflammatory responses.

AIMS: CKbeta8/CCL23 is a CC chemokine and alternative splicing of the CKbeta8 gene produces two mRNAs that encode CKbeta8 and its isoform CKbeta8-1. Although it has been reported that CKbeta8 and CKbeta8-1 are implicated in leukocyte trafficking and development of inflammation, the exact roles of these two chemokines in immune responses and the associated chemotaxis signaling are still obscure. MAIN
METHODS: To understand the mechanism of CKbeta8- and CKbeta8-1-induced chemotaxis signaling, we examined the chemotactic activities of osteogenic sarcoma cells expressing CC chemokine receptor 1 in response to CKbeta8 and CKbeta8-1. We also examined involvement of CKbeta8 and CKbeta8-1 in inflammatory responses by determining the mRNA expression of pro-inflammatory molecules induced by two chemokines and expressions of these chemokines in foam cells. KEY
FINDINGS: Results from a chemotaxis assay using various inhibitors for signaling molecules showed that the chemotaxis signal pathway induced by both CKbeta8 and CKbeta8-1 was mediated via the G(i)/G(o) protein, phospholipase C (PLC) and protein kinase Cdelta (PKCdelta). Treatment with a nuclear factor kappaB (NF-kappaB) inhibitor reduced the chemotactic activities of CKbeta8 and CKbeta8-1, and NF-kappaB was activated in response to CKbeta8 and CKbeta8-1. In addition, CKbeta8 and CKbeta8-1 increased mRNA expression of pro-inflammatory cytokines and adhesion molecules. The mRNA levels of CKbeta8 and CKbeta8-1 were increased in foam cells. SIGNIFICANCE: These results indicate that both CKbeta8 and CKbeta8-1 transduce the chemotaxis signal through the G(i)/G(o) protein, PLC, PKCdelta, and NF-kappaB, and that CKbeta8 and CKbeta8-1 probably play important roles in inflammatory diseases such as atherosclerosis. Copyright 2009 Elsevier Inc. All rights reserved.