Abstract
Aims CKβ8/CCL23 is a CC chemokine and alternative splicing of the CKβ8 gene produces two mRNAs that encode CKβ8 and its isoform CKβ8-1. Although it has been reported that CKβ8 and CKβ8-1 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 CKβ8- and CKβ8-1-induced chemotaxis signaling, we examined the chemotactic activities of osteogenic sarcoma cells expressing CC chemokine receptor 1 in response to CKβ8 and CKβ8-1. We also examined involvement of CKβ8 and CKβ8-1 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 CKβ8 and CKβ8-1 was mediated via the G i/G o protein, phospholipase C (PLC) and protein kinase Cδ (PKCδ). Treatment with a nuclear factor κB (NF-κB) inhibitor reduced the chemotactic activities of CKβ8 and CKβ8-1, and NF-κB was activated in response to CKβ8 and CKβ8-1. In addition, CKβ8 and CKβ8-1 increased mRNA expression of pro-inflammatory cytokines and adhesion molecules. The mRNA levels of CKβ8 and CKβ8-1 were increased in foam cells. Significance These results indicate that both CKβ8 and CKβ8-1 transduce the chemotaxis signal through the G i/G o protein, PLC, PKCδ, and NF-κB, and that CKβ8 and CKβ8-1 probably play important roles in inflammatory diseases such as atherosclerosis.
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