Genomic organization, sequence analysis and transcriptional regulation of the human MCP-4 chemokine gene (SCYA13) in dermal fibroblasts: A comparisonto other eosinophilic beta-chemokines

The eosinophil chemotactic beta-chemokine MCP-4 is assumed to be involved i n the accumulation of eosinophils characteristic for eosinophilic inflammat ory diseases. We here describe the genomic organisation (3 exons of 138, 11 5 and 578 bp, 2 introns of 867 and 437 bp and 1.4 kb of regulatory sequence s from the immediate 5' upstream region), sequence (genomic and transcribed ) and mRNA expression of the human MCP-4 gene in dermal fibroblasts. Among the promoter elements potentially regulating MCP-4 gene expression and/or m ediating the effects of antiinflammatory drugs we identified consensus sequ ences known to interact with nuclear factors like NF-IL6, AP-2, a NF-kappa B like consensus sequence, gamma-interferon- response and W-l elements as w ell as glucocorticoid response elements. Like MCP-3, MCP-4 mRNA expression in dermal fibroblasts is upregulated by TNF-alpha, IL-1 alpha, IFN-gamma or IL-4 and differs from RANTES and eotaxin mRNA expression in its response t o IFN-gamma and/or IL-4, (C) 1999 Academic Press.