Modulation of intercellular communication between smooth muscle cells by growth factors and cytokines.
We recently reported that tumor necrosis factor alpha is able to cause a dose-dependent and persistent reduction in gap junctional intercellular communication between primary human smooth muscle cells. In order to study whether this observed persistent reduction in gap junctional intercellular communication is a unique feature for tumor necrosis factor alpha, the present study focuses on the effects of other growth factors and cytokines on gap junctional intercellular communication. Platelet-derived growth factor AA and BB (PDGF-AA, PDGF-BB), basic fibroblast growth factor (bFGF), interleukin-6 and interferon-gamma were able to modulate gap junctional intercellular communication between primary human smooth muscle cells in vitro. However, our results demonstrate that the magnitude and nature of the observed effects are growth factor- and cytokine-specific. PDGF-AA, PDGF-BB and interleukin-6 caused a transient reduction in gap junctional intercellular communication, while bFGF induced a transient increase in gap junctional intercellular communication. Interferon-gamma was shown to be capable of causing a persistent reduction in gap junctional intercellular communication. In addition, PDGF-AA, PDGF-BB, bFGF, interleukin-6, interferon-gamma and tumor necrosis factor alpha all stimulated smooth muscle cell proliferation. These observations suggest a more complex relationship between modulation of gap junctional intercellular communication and cell proliferation than current hypotheses imply. The implications of the observed effects of growth factors and cytokines on gap junctional intercellular communication between smooth muscle cells in relation to the process of atherosclerosis is discussed.
Mensink
A
A
Department of Toxicology, Agricultural University Wageningen, Netherlands.
Brouwer
A
A
Van den Burg
E H
EH
Geurts
S
S
Jongen
W M
WM
Lakemond
C M
CM
Meijerman
I
I
Van der Wijk
T
T
D001161:Arteriosclerosis / Q000139:chemically induced / Q000209:etiology; D000077214:Becaplermin; D002450:Cell Communication / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured / Q000187:drug effects; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D006801:Humans; D007365:Intercellular Junctions / Q000187:drug effects* / Q000502:physiology; D007371:Interferon-gamma / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000502:physiology
D015850:Interleukin-6; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D014409:Tumor Necrosis Factor-alpha; C075278:platelet-derived growth factor A; D000077214:Becaplermin; D005346:Fibroblast Growth Factors; D007371:Interferon-gamma