Hydrogen sulfide potentiates interleukin-1beta-induced nitric oxide production via enhancement of extracellular signal-regulated kinase activation in rat vascular smooth muscle cells.
Hydrogen sulfide (H(2)S) and nitric oxide (NO) are endogenously synthesized from l-cysteine and l-arginine, respectively. They might constitute a cooperative network to regulate their effects. In this study, we investigated whether H(2)S could affect NO production in rat vascular smooth muscle cells (VSMCs) stimulated with interleukin-1beta (IL-1beta). Although H(2)S by itself showed no effect on NO production, it augmented IL-beta-induced NO production and this effect was associated with increased expression of inducible NO synthase (iNOS) and activation of nuclear factor (NF)-kappaB. IL-1Beta activated the extracellular signal-regulated kinase 1/2 (ERK1/2), and this activation was also enhanced by H(2)S. Inhibition of ERK1/2 activation by the selective inhibitor U0126 inhibited IL-1beta-induced NF-kappaB activation, iNOS expression, and NO production either in the absence or presence of H(2)S. Our findings suggest that H(2)S enhances NO production and iNOS expression by potentiating IL-1beta-induced NF-kappaB activation through a mechanism involving ERK1/2 signaling cascade in rat VSMCs.
Jeong
Sun-Oh
SO
Medicinal Resources Research Institute, Wonkwang University, Department of Microbiology and Immunology, Wonkwang University School of Medicine, Chonbug 570-749, Republic of Korea.
Pae
Hyun-Ock
HO
Oh
Gi-Su
GS
Jeong
Gil-Saeng
GS
Lee
Bok-Soo
BS
Lee
Seoul
S
Kim
Du Yong
du Y
Rhew
Hyun Yul
HY
Lee
Kang-Min
KM
Chung
Hun-Taeg
HT
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D002070:Butadienes / Q000494:pharmacology; D002478:Cells, Cultured; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D007375:Interleukin-1 / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000201:enzymology*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D051381:Rats
D002070:Butadienes; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D009570:Nitriles; C113580:U 0126; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D006862:Hydrogen Sulfide