PMID- 10843667
OWN - NLM
STAT- MEDLINE
DCOM- 20000720
LR  - 20220309
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 164
IP  - 12
DP  - 2000 Jun 15
TI  - Monocyte chemoattractant protein-1 enhances gene expression and synthesis of 
      matrix metalloproteinase-1 in human fibroblasts by an autocrine IL-1 alpha loop.
PG  - 6174-9
AB  - Monocyte chemoattractant protein-1 (MCP-1), a member of the C-C chemokine 
      superfamily, has recently been shown to be involved in the pathogenesis of tissue 
      fibrosis. In vitro studies demonstrated that MCP-1 up-regulates type I collagen 
      gene expression via endogenous production of TGF-beta in rat lung fibroblasts. We 
      here show that recombinant human MCP-1 affects gene expression of interstitial 
      collagenase (matrix metalloproteinase-1 (MMP-1)) in primary human skin 
      fibroblasts and a stable fibroblast cell line. MMP-1 mRNA was induced by MCP-1 
      (10 ng/ml) as early as 6 h and reached a maximal expression at 24 h. MCP-1 also 
      caused an increase of MMP-2 mRNA expression in both types of fibroblasts at 48 h. 
      Interestingly, tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA was also 
      up-regulated by MCP-1, and TIMP-1 mRNA expression peaked at 48 h in both types of 
      fibroblasts. Immunoblot analysis demonstrated increased levels of MMP-1 and 
      TIMP-1 protein in the culture supernatants of primary fibroblasts stimulated with 
      MCP-1. In addition, MCP-1 strongly induced IL-1 alpha mRNA expression in dermal 
      fibroblasts in parallel with the induction of MMP-1. Preincubation with IL-1 
      receptor antagonist almost completely abrogated the expression of MMP-1 mRNA, and 
      partially inhibited MMP-1 synthesis induced by MCP-1. Transient transfection of 
      primary skin fibroblasts with a MMP-1 promoter-reporter construct indicated a 
      dose-dependent increase in promoter activity by MCP-1 stimulation. These data 
      demonstrate that MCP-1 up-regulates MMP-1 mRNA expression and synthesis in human 
      skin fibroblasts at a transcriptional level and provide evidence that this is 
      mediated by an IL-1 alpha autocrine loop.
FAU - Yamamoto, T
AU  - Yamamoto T
AD  - Department of Dermatology, University of Cologne, Germany. 
      yamamoto.derm@med.tmd.ac.jp
FAU - Eckes, B
AU  - Eckes B
FAU - Mauch, C
AU  - Mauch C
FAU - Hartmann, K
AU  - Hartmann K
FAU - Krieg, T
AU  - Krieg T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Chemokine CCL2)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Interleukin-1)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.7 (Matrix Metalloproteinase 1)
SB  - IM
MH  - Autocrine Communication/*immunology
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/metabolism/*physiology
MH  - Culture Media, Conditioned/chemistry
MH  - Fibroblasts/*enzymology/*immunology/metabolism
MH  - Gene Expression Regulation/*immunology
MH  - Humans
MH  - Interleukin-1/*physiology
MH  - Matrix Metalloproteinase 1/*biosynthesis/*genetics/isolation & purification
MH  - Matrix Metalloproteinase 2/biosynthesis/genetics
MH  - RNA, Messenger/biosynthesis
MH  - Tissue Inhibitor of Metalloproteinase-1/biosynthesis/genetics/isolation & 
      purification
MH  - Transcriptional Activation/immunology
MH  - Up-Regulation/immunology
EDAT- 2000/06/08 09:00
MHDA- 2000/07/25 11:00
CRDT- 2000/06/08 09:00
PHST- 2000/06/08 09:00 [pubmed]
PHST- 2000/07/25 11:00 [medline]
PHST- 2000/06/08 09:00 [entrez]
AID - ji_v164n12p6174 [pii]
AID - 10.4049/jimmunol.164.12.6174 [doi]
PST - ppublish
SO  - J Immunol. 2000 Jun 15;164(12):6174-9. doi: 10.4049/jimmunol.164.12.6174.