Genomic organization, sequence analysis and transcriptional regulation of the human MCP-4 chemokine gene (SCYA13) in dermal fibroblasts: a comparison to other eosinophilic beta-chemokines.
The eosinophil chemotactic beta-chemokine MCP-4 is assumed to be involved in the accumulation of eosinophils characteristic for eosinophilic inflammatory diseases. We here describe the genomic organisation (3 exons of 138, 115 and 578 bp, 2 introns of 867 and 437 bp and 1.4 kb of regulatory sequences 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 mediating the effects of anti-inflammatory drugs we identified consensus sequences known to interact with nuclear factors like NF-IL6, AP-2, a NF-kappaB like consensus sequence, gamma-interferon- response and YY-1 elements as well as glucocorticoid response elements. Like MCP-3, MCP-4 mRNA expression in dermal fibroblasts is upregulated by TNF-alpha, IL-1alpha, IFN-gamma or IL-4 and differs from RANTES and eotaxin mRNA expression in its response to IFN-gamma and/or IL-4.
Hein
H
H
Clinical Research Unit, Department of Dermatology, University of Kiel, Germany.
Schlüter
C
C
Kulke
R
R
Christophers
E
E
Schröder
J M
JM
Bartels
J
J
D020121:5' Untranslated Regions / Q000737:chemistry; D000595:Amino Acid Sequence; D001483:Base Sequence; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000737:chemistry / Q000235:genetics*; D004804:Eosinophils / Q000502:physiology*; D005091:Exons; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D018945:Monocyte Chemoattractant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D012045:Regulatory Sequences, Nucleic Acid; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000166:cytology; D014158:Transcription, Genetic
D020121:5' Untranslated Regions; C099677:CCL13 protein, human; D019742:Chemokines, CC; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger