PMID- 9529162
OWN - NLM
STAT- MEDLINE
DCOM- 19980409
LR  - 20190706
IS  - 0009-7330 (Print)
IS  - 0009-7330 (Linking)
VI  - 82
IP  - 5
DP  - 1998 Mar 23
TI  - Expression and regulation of adhesion molecules in cardiac cells by cytokines: 
      response to acute hypoxia.
PG  - 576-86
AB  - Adhesion molecules mediate inflammatory myocardial injury after 
      ischemia/reperfusion. Cytokine release and hypoxia are features of acute ischemia 
      that may influence expression of these molecules. Accordingly, we studied 
      intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) 
      responses to cytokines and acute hypoxia in cultured myocardial cells. Northern 
      blot analysis and immunoassay showed that the proinflammatory cytokines 
      interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha stimulated 
      concentration-dependent increases in ICAM and VCAM mRNA and protein. In both 
      cardiac myocytes and fibroblasts, pretreatment with a specific inhibitor of 
      nuclear transcription factor-kappaB (NF-kappaB) prevented cytokine induction of 
      both molecules. We also found that inhibition of tyrosine kinase and p38/RK 
      (stress-activated protein kinase) pathways prevented IL-1beta-induced ICAM and 
      VCAM protein synthesis, whereas extracellular signal-regulated protein kinase 
      (ERK1/ERK2) inhibition did not. Neither hypoxia (0% O2 for 6 hours) alone nor 
      hypoxia/reoxygenation had any significant effect on ICAM and VCAM mRNA. However, 
      hypoxia did enhance IL-1beta-induced ICAM mRNA expression in myocytes. As a 
      possible mechanism of this synergistic action on CAM expression, hypoxia induced 
      a time-dependent increase in the DNA binding activity of both NF-kappaB and 
      activator protein-1 (AP-1), two transcription factors important for cell adhesion 
      molecule expression. In contrast to the enhanced ICAM mRNA induced by IL-1beta 
      during hypoxia, however, protein levels for this adhesion molecule were unchanged 
      beyond IL-1beta-stimulated levels, suggesting posttranscriptional and/or 
      posttranslational control mechanisms. We conclude that cytokines regulate ICAM 
      and VCAM mRNA and protein in both cardiac myocytes and fibroblasts. Furthermore, 
      adhesion molecule induction requires translocation of at least two transcription 
      factors, NF-kappaB and AP-1.
FAU - Kacimi, R
AU  - Kacimi R
AD  - Veterans Affairs Medical Center, the Cardiovascular Research Institute, and the 
      Department of Medicine, University of California, San Francisco 94121, USA.
FAU - Karliner, J S
AU  - Karliner JS
FAU - Koudssi, F
AU  - Koudssi F
FAU - Long, C S
AU  - Long CS
LA  - eng
GR  - HL-25847/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Interleukin-1)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Animals
MH  - Cell Hypoxia/physiology
MH  - Cells, Cultured
MH  - Cyclic AMP/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Gene Expression Regulation/drug effects
MH  - Intercellular Adhesion Molecule-1/*genetics/metabolism
MH  - Interleukin-1/*pharmacology
MH  - Monocytes/cytology
MH  - Myocardium/chemistry/*cytology/enzymology
MH  - NF-kappa B/metabolism
MH  - Protein Kinase C/metabolism
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/physiology
MH  - Time Factors
MH  - Transcription Factor AP-1/metabolism
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Vascular Cell Adhesion Molecule-1/*genetics/metabolism
EDAT- 1998/04/07 00:00
MHDA- 1998/04/07 00:01
CRDT- 1998/04/07 00:00
PHST- 1998/04/07 00:00 [pubmed]
PHST- 1998/04/07 00:01 [medline]
PHST- 1998/04/07 00:00 [entrez]
AID - 10.1161/01.res.82.5.576 [doi]
PST - ppublish
SO  - Circ Res. 1998 Mar 23;82(5):576-86. doi: 10.1161/01.res.82.5.576.