Nitric Oxide Regulation of IL-8 Expression in Human Endothelial Cells

Villarete, Lorelie; Remick, Daniel G.

doi:10.1006/bbrc.1995.1864

Cited by 74 publications

(29 citation statements)

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“…The dose of 20 mM of L-NAME which we used in this study seems to be relatively high. However, same concentration was adopted in other studies [17,18] and was also necessary for inhibition of radiation-induced NOS activation in ex vivo samples from SCCVII tumors in our previous report [3]. In this experiment, L-NAME at 20 mM showed significant inhibition against the increase of NOS activity induced by X-irradiation, but substantial NO activity still remained; the enzyme responsible for this rest activity was unclear at present.…”

Section: Discussionmentioning

confidence: 76%

Activation of eNOS in endothelial cells exposed to ionizing radiation involves components of the DNA damage response pathway

Nagane

Yasui

Sakai

et al. 2015

Biochemical and Biophysical Research Communications

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In this study, the involvement of ataxia telangiectasia mutated (ATM) kinase and heat shock protein 90 (HSP90) in endothelial nitric oxide synthase (eNOS) activation was investigated in X-irradiated bovine aortic endothelial cells. The activity of nitric oxide synthase (NOS) and the phosphorylation of serine 1179 of eNOS (eNOS-Ser1179) were significantly increased in irradiated cells. The radiation-induced increases in NOS activity and eNOS-Ser1179 phosphorylation levels were significantly reduced by treatment with either an ATM inhibitor (Ku-60019) or an HSP90 inhibitor (geldanamycin). Geldanamycin was furthermore found to suppress the radiation-induced phosphorylation of ATM-Ser1181. Our results indicate that the radiation-induced eNOS activation in bovine aortic endothelial cells is regulated by ATM and HSP90.

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Section: Discussionmentioning

confidence: 76%

Activation of eNOS in endothelial cells exposed to ionizing radiation involves components of the DNA damage response pathway

Nagane

Yasui

Sakai

et al. 2015

Biochemical and Biophysical Research Communications

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“…Nitric oxide has also been associated with the regulation of gene expression in endothelial cells (51)(52)(53)(54). Activation of p38 has also been associ- ated with transcription factor activation (1,8).…”

Section: Discussionmentioning

confidence: 99%

Activation of p38 Mitogen-activated Protein Kinase by Lipopolysaccharide in Human Neutrophils Requires Nitric Oxide-dependent cGMP Accumulation

Browning¹,

Windes

1999

Journal of Biological Chemistry

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This study examined the signal transduction pathway(s) leading to phosphorylation of p38 in human neutrophils stimulated with lipopolysaccharide and formyl peptides. Blockade of the nitric oxide (NO) pathway in neutrophils with the NO synthase inhibitor N-nitro-Larginine methyl ester or by treatment with the NO scavenger 2-phenyl-tetramethylimidazoline-1-oxyl-3-oxide attenuated phosphorylation of the mitogen-activated protein kinase p38 in response to lipopolysaccharide but not fMet-Leu-Phe. Using the NO releasing agents S-nitroso-N-acetylpenicillamine and sodium nitroprusside it was determined that nitric oxide is sufficient to cause an increase in phosphorylation of p38. Increasing cellular cGMP with phosphodiesterase inhibitors, by stimulation of soluble guanylyl cyclase with YC-1 or with exogenous dibutyryl cGMP resulted in mitogenactivated protein kinase/extracellular signal-regulated kinase kinase 3,6 (MEK3,6) activation and phosphorylation of p38. This phenomenon was specific for MEK3,6, because these agents had no effect on the phosphorylation state of MEK1,2. A role for protein kinase G but not protein kinase A downstream of lipopolysaccharide but not formylmethionylleucylphenylalanine was shown using the specific inhibitors KT5823 and H89, respectively. These data indicate that activation of p38 by fMet-LeuPhe and lipopolysaccharide involve different mechanisms, and that activation of protein kinase G by NO-dependent stimulation of guanylyl cyclase is necessary and sufficient for phosphorylation of p38 downstream of lipopolysaccharide.Detection of microbial products such as lipopolysaccharide (LPS) 1 and N-formyl peptides (fMLF) by neutrophils is an essential event that triggers the microbicidal functions of these cells. Activation of neutrophils by such stimuli results in chemotaxis to inflammatory sites, cytokine production, release of degradative granule enzymes, and generation of toxic oxygen intermediates.The MAP kinases are members of discrete signaling cascades that form focal points for diverse extracellular stimuli and function to regulate fundamental cellular processes. Three distinct classes within the MAP kinase family have been described, including ERK, c-jun-NH 2 kinase, and p38, each having different physiological roles (1-4). The p38 MAP kinase is associated with immune cell activation, because this kinase is activated by a variety of inflammatory mediators (5, 6). It is well established that p38 has an important role in gene expression in monocytes and macrophages (7-9). A specific function for p38 in neutrophils remains unclear, but it has been suggested to play an important role in the respiratory burst, interleukin 8 production, and apoptosis (10 -13). Activation of p38 occurs after phosphorylation of a distinctive TGY motif by the upstream kinases MEK3 or MEK6 (6, 14 -16). Stimulation of human neutrophils with classical chemoattractants, including fMLF, results in a rapid and transient phosphorylation and activation of p38 (12,13,(17)(18)(19)(20). It has also been demonstrated th...

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“…They showed that the process of malignant transformation induced modifications in the activities of signal transduction pathways activated by cytokines, such as an increase in ERK phosphorilation, and that these modifications were similar to those seen in established lung cancer cell lines (Loewen et al, 2005). Studies on the modulation of IL-8 synthesis by endothelial cells induced by NO • have yielded opposite results when normal human endothelial cells (De Caterina et al, 1995) and cells of the line ECV304 were used (Villarete and Remick, 1995), showing an inhibition and an upregulation of IL-8 synthesis, respectively. Thus, the apparent discrepancy between our results and those obtained by Sparkman is likely due, at least in part, to differences in the cell model.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, however, numerous biological activities besides vascular relaxation have been attributed to NO • . Many of these activities are related to the regulation of the inflammatory process, including modulation of the synthesis of cytokines by endothelial cells (De Caterina et al, 1995, Villarete and Remick, 1995, Natarajan et al, 2001 and by monocytes/macrophages (Lander et al, 1993, Ma et al, 2004, down-regulation of neutrophil aggregation and secretion (May et al, 1991), down-regulation of the release of inflammatory mediators by mast cells (van Overveld et al, 1993), prevention of superoxide production by neutrophils (Clancy et al, 1992). NO • is synthesized from L-arginine through the action of a family of enzymes called NO • synthases (NOS).…”

Section: Introductionmentioning

confidence: 99%