PMID- 10435007
OWN - NLM
STAT- MEDLINE
DCOM- 19990819
LR  - 20190513
IS  - 0008-6363 (Print)
IS  - 0008-6363 (Linking)
VI  - 42
IP  - 1
DP  - 1999 Apr
TI  - Proinflammatory cytokines regulate tissue inhibitors of metalloproteinases and
      disintegrin metalloproteinase in cardiac cells.
PG  - 162-72
AB  - OBJECTIVE: Tissue inhibitors of metalloproteinases (TIMPs) are downregulated in
      the failing human heart. The objective of the present study was to test the
      hypothesis that cytokines might be involved in the regulation of TIMPs in cardiac
      cells. METHODS: Neonatal Sprague-Dawley rat ventricular cells were exposed to 100
      units/ml tumor necrosis factor-alpha and/or 5 ng/ml interleukin-1 beta. The mRNA 
      and protein expression of TIMPs-1-4 and disintegrin metalloproteinase was
      analyzed using Northern blot, ELISA and/or Western blot, respectively.
      Proteolytic activity and extracellular matrix degradation and turnover were
      determined using gelatin zymography and pulse-chase experiments. RESULTS: The
      TIMP-1 mRNA was upregulated in cardiac cells, while TIMP-1 protein levels were
      unchanged in myocytes but downregulated in non-myocytes. The TIMP-2 expression
      did not change with the cytokine treatment. TIMP-3 was downregulated at both the 
      mRNA and protein levels in cardiac cells. TIMP-4 protein was transiently
      increased and then returned to control level. In contrast, disintegrin
      metalloproteinase mRNA and protein were significantly upregulated in those cells.
      The gelatinolytic activity and extracellular matrix protein degradation were
      significantly increased. CONCLUSIONS: Tumor necrosis factor-alpha and
      interleukin-1 beta regulate the expression of TIMPs and disintegrin
      metalloproteinase, which may in turn contribute to the increased matrix
      degradation in cardiac cells. Since heart failure in humans is characterized by
      both re-expression of myocardial cytokines and remodeling of the extracellular
      matrix, those in vitro results suggest a potential role for those cytokines in
      the regulation of extracellular matrix remodeling and therefore in the transition
      to the end-stage heart failure phenotype.
FAU - Li, Y Y
AU  - Li YY
AD  - Research Laboratories, University of Pittsburgh School of Medicine, PA 15213,
      USA.
FAU - McTiernan, C F
AU  - McTiernan CF
FAU - Feldman, A M
AU  - Feldman AM
LA  - eng
GR  - HL60032-01/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (Cytokines)
RN  - 0 (Disintegrins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Interleukin-1)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-3)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (tissue inhibitor of metalloproteinase-4)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - EC 3.4.24.- (Metalloendopeptidases)
SB  - IM
MH  - Animals
MH  - Blotting, Northern
MH  - Cells, Cultured
MH  - Cytokines/*pharmacology
MH  - Disintegrins/*metabolism
MH  - Enzyme Inhibitors/metabolism
MH  - Extracellular Matrix/metabolism
MH  - Gene Expression/drug effects
MH  - Heart Failure/metabolism
MH  - Interleukin-1/pharmacology
MH  - Metalloendopeptidases/*metabolism
MH  - Myocardium/*metabolism
MH  - RNA, Messenger/analysis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tissue Inhibitor of Metalloproteinase-1/genetics/metabolism
MH  - Tissue Inhibitor of Metalloproteinase-2/genetics/metabolism
MH  - Tissue Inhibitor of Metalloproteinase-3/genetics/metabolism
MH  - Tissue Inhibitor of Metalloproteinases/genetics/*metabolism
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 1999/08/06 00:00
MHDA- 1999/08/06 00:01
CRDT- 1999/08/06 00:00
PHST- 1999/08/06 00:00 [pubmed]
PHST- 1999/08/06 00:01 [medline]
PHST- 1999/08/06 00:00 [entrez]
AID - S0008-6363(98)00297-1 [pii]
AID - 10.1016/s0008-6363(98)00297-1 [doi]
PST - ppublish
SO  - Cardiovasc Res. 1999 Apr;42(1):162-72. doi: 10.1016/s0008-6363(98)00297-1.