Molecular cloning of the MCP-3 chemokine gene and regulation of its expression

Eur Cytokine Netw. Mar-Apr 1993;4(2):99-110.

Abstract

We have isolated a cDNA (NC28) transcribed from a mRNA which is transiently induced in U937 promonocytic cells by PMA and super-induced by cycloheximide. NC28 cDNA encodes a new member of the chemokine family, MCP-3, recently purified from MG-63 osteosarcoma cells by Van Damme et al. [1]. The MCP-3 protein sequence shows 74% identity with human monocyte chemoattractant protein 1 (MCP-1) and, like MCP-1, recombinant MCP-3 protein shows chemotactic activity for monocytes but not for neutrophils. However the secreted MCP-3 protein differs from MCP-1 in being N-glycosylated. The 3' noncoding regions of MCP-3 and MCP-1 mRNAs are more diverged (44%), allowing specific cDNA probes to be made, and indicating that the two genes are evolutionarily distant. Sequence comparisons of the 3' noncoding regions suggest that MCP-3 may be the human homologue of the mouse MARC gene [2], and that MCP-1 and MCP-3 genes arose by a gene duplication event before the mammalian radiation. Both MCP-1 and MCP-3 mRNAs are expressed by PBMC, principally by monocytes, with MCP-1 mRNA being expressed at levels 2-4 times that of MCP-3 mRNA. However, while MCP-1 mRNA is also expressed at high levels in fibroblast or astrocytoma cell lines after IL-1 and TNF stimulation, MCP-3 mRNA is expressed only at very low levels in these cells. The cellular origin of MCP-3 is thus more restricted than that of MCP-1. In our experiments on PBMC, LPS is not a consistent inducer of MCP-1 and MCP-3 mRNAs. In some experiments, it actually decreases levels of these two mRNAs, while concomitantly increasing IL-6 and TNF-alpha mRNA levels. Levels of MCP-1 and MCP-3 mRNAs in PBMC are both increased by IFN-gamma, although IL-6 mRNA is not induced. They are also increased by PHA-P and are decreased, in most cases, by IL-13 [3]. MCP-1 and MCP-3 mRNAs are thus co-ordinately regulated in monocytes in response to a number of inducing or inhibitory agents, in a manner differing in several respects from that of other monokines such as IL-6.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Biological Evolution
  • Cells, Cultured
  • Chemokine CCL7
  • Chemotactic Factors / genetics*
  • Cloning, Molecular
  • Cytokines*
  • DNA / genetics
  • Gene Expression Regulation
  • Humans
  • Mice
  • Molecular Sequence Data
  • Monocyte Chemoattractant Proteins*
  • Monocytes / immunology
  • RNA, Messenger / genetics
  • Rats
  • Sequence Homology, Amino Acid
  • Species Specificity

Substances

  • CCL7 protein, human
  • Ccl7 protein, mouse
  • Ccl7 protein, rat
  • Chemokine CCL7
  • Chemotactic Factors
  • Cytokines
  • Monocyte Chemoattractant Proteins
  • RNA, Messenger
  • DNA

Associated data

  • GENBANK/L09679
  • GENBANK/L09680
  • GENBANK/L09681
  • GENBANK/L09682
  • GENBANK/L09683
  • GENBANK/L16554
  • GENBANK/L16555
  • GENBANK/L16556
  • GENBANK/S67456
  • GENBANK/X71087