Growth factors enhance interleukin-1 beta-induced persistent activation of nuclear factor-kappa B in rat vascular smooth muscle cells.
OBJECTIVE
Activation of extracellular signal-regulated kinases (ERKs) is required for interleukin-1beta to persistently activate nuclear factor (NF)-kappaB and concomitantly express inducible NO synthase (iNOS) in rat vascular smooth muscle cells (VSMCs). The present study examined whether platelet-derived growth factor (PDGF) or epidermal growth factor (EGF) could influence the VSMC response to interleukin-1beta via an ERK-related signaling pathway.


RESULTS
Treatment of VSMCs with PDGF or EGF alone potently induced ERK phosphorylation and DNA synthesis but did not induce NF-kappaB activation or iNOS expression. However, either PDGF or EGF markedly enhanced interleukin-1beta-induced persistent NF-kappaB activation and iNOS expression but did not affect the early and transient NF-kappaB activation. Growth factor-induced DNA synthesis was attenuated in the presence of interleukin-1beta. Inhibition of ERK phosphorylation with selective inhibitors (PD98059 or U0126) attenuated interleukin-1beta-induced persistent NF-kappaB activation and iNOS expression in either the absence or presence of the growth factors.


CONCLUSIONS
These results indicate that interleukin-1beta-induced expression of NF-kappaB-dependent genes, such as iNOS, is potentiated in the presence of growth factors through a mechanism requiring ERK-dependent enhanced NF-kappaB activation, and the results also suggest that NF-kappaB activation is not required for PDGF or EGF to trigger DNA synthesis in VSMCs.
Jiang
Bingbing
B
Vascular Biology Unit, Whitaker Cardiovascular Institute, Department of Medicine, Boston University School of Medicine, Boston, Mass 02118, USA. bjiang@bu.edu
Xu
Shanqin
S
Brecher
Peter
P
Cohen
Richard A
RA
D000818:Animals; D001013:Aorta, Thoracic / Q000737:chemistry / Q000166:cytology / Q000201:enzymology; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D004815:Epidermal Growth Factor / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism*; D007375:Interleukin-1 / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000737:chemistry* / Q000166:cytology / Q000201:enzymology; D016328:NF-kappa B / Q000378:metabolism* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000502:physiology
D006133:Growth Substances; D007375:Interleukin-1; D016328:NF-kappa B; D009573:Nitrites; D010982:Platelet-Derived Growth Factor; D004815:Epidermal Growth Factor; D004247:DNA; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D020928:Mitogen-Activated Protein Kinases