CKΒ8/CCL23 induces cell migration via the Gi/Go protein/PLC/PKCδ/NF-κB and is involved in inflammatory responses

Jeonghan Kim, Yoon Suk Kim, Jesang Ko

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 Gi/Go 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 Gi/Go protein, PLC, PKCδ, and NF-κB, and that CKΒ8 and CKΒ8-1 probably play important roles in inflammatory diseases such as atherosclerosis.

Original languageEnglish
Pages (from-to)300-308
Number of pages9
JournalLife Sciences
Volume86
Issue number9-10
DOIs
Publication statusPublished - 2010 Feb

Keywords

  • Atherosclerosis
  • CKΒ8
  • Chemokine
  • Chemotaxis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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