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


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.


RESULTS
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.


CONCLUSIONS
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.
Kim
Jeonghan
J
School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, South Korea.
Kim
Yoon Suk
YS
Ko
Jesang
J
D002478:Cells, Cultured; D019742:Chemokines, CC / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology*; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology*; D051745:Protein Kinase C-delta / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000502:physiology*
C105504:CCL23 protein, human; D019742:Chemokines, CC; D018836:Inflammation Mediators; D016328:NF-kappa B; D051745:Protein Kinase C-delta; D010738:Type C Phospholipases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go