PMID- 10353468
OWN - NLM
STAT- MEDLINE
DCOM- 19990715
LR  - 20161018
IS  - 1434-6621 (Print)
IS  - 1434-6621 (Linking)
VI  - 37
IP  - 3
DP  - 1999 Mar
TI  - Mycophenolic acid influences T helper 2 (Th2) cytokine induced expression of 
      intercellular cell adhesion molecule-1 (ICAM-1) on human endothelial cells.
PG  - 253-7
AB  - A possible synergistic effect of mycophenolic acid (MPA) and the 
      immunosuppressive cytokines IL-4, IL-10 and IL-13 was investigated in human 
      umbilical vein endothelial cells (HUVEC). These cytokines, which are produced by 
      Th2-lymphocytes, were shown to induce the expression of vascular cell adhesion 
      molecule-1 (VCAM-1) and production of IL-6 in endothelial cells. In this study we 
      found IL-4 to induce both intercellular cell adhesion molecule-1 (ICAM-1) and 
      VCAM-1 expression, whereas IL-13 induced VCAM-1 only. The surface expression of 
      E-selectin was not influenced by any of the cytokines tested. MPA on its own led 
      to statistically significant ICAM-1 expression on HUVEC. The combination of MPA 
      with IL-4 led to a significant ICAM-1 expression in an additive manner compared 
      to the cytokine alone. In contrast, MPA neither induced VCAM-1 nor did it 
      influence the effects of IL-4 and IL-13 on VCAM-1 expression. A clinically 
      relevant concentration of mycophenolic acid (10 micromol/l) decreased 
      intracellular guanosine-5'-triphosphate (GTP) levels significantly. Since 
      intracellular nucleotides are responsible for the glycosylation of proteins, a 
      disturbance of the endothelial nucleotide balance could be responsible for the 
      effects of MPA on ICAM-1. Guanine and guanosine prevented and partially reversed 
      the actions of MPA, on both intracellular GTP and ICAM-1 expression, which 
      strongly implies that MPA by interfering with nucleotide metabolism, affects the 
      adhesive properties of endothelial cells, and by acting synergistically with IL-4 
      probably influences Th2 cytokine effects.
FAU - Weigel, G
AU  - Weigel G
AD  - Department of Cardiothoracic Surgery, University Vienna, Austria. 
      guenter.weigel@akh-wien.ac.at
FAU - Bertalanffy, P
AU  - Bertalanffy P
FAU - Dubsky, P
AU  - Dubsky P
FAU - Griesmacher, A
AU  - Griesmacher A
FAU - Wolner, E
AU  - Wolner E
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Clin Chem Lab Med
JT  - Clinical chemistry and laboratory medicine
JID - 9806306
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Interleukins)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - HU9DX48N0T (Mycophenolic Acid)
SB  - IM
MH  - Cell Adhesion Molecules/metabolism
MH  - Cells, Cultured
MH  - Endothelium, Vascular/*drug effects/metabolism
MH  - Guanosine Triphosphate/metabolism
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/*metabolism
MH  - Interleukins/*physiology
MH  - Mycophenolic Acid/*pharmacology
MH  - Th2 Cells/*drug effects/metabolism
EDAT- 1999/06/03 00:00
MHDA- 1999/06/03 00:01
CRDT- 1999/06/03 00:00
PHST- 1999/06/03 00:00 [pubmed]
PHST- 1999/06/03 00:01 [medline]
PHST- 1999/06/03 00:00 [entrez]
AID - 10.1515/CCLM.1999.044 [doi]
PST - ppublish
SO  - Clin Chem Lab Med. 1999 Mar;37(3):253-7. doi: 10.1515/CCLM.1999.044.