Regulation of inducible no synthase expression by endothelin in primary cultured glial cells

Murayama, Toshihiko; Oda, Haruko; Sasaki, Yukio; Okada, Toshikazu; Nomura, Yasuyuki

doi:10.1016/s0024-3205(98)00095-2

Cited by 9 publications

(3 citation statements)

References 14 publications

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“…3 and 4). These results suggest that the role of ET-1 in the regulation of iNOS gene expression is tissue specific because ET-1 seems to enhance iNOS gene expression in the liver whereas it inhibits iNOS expression in the kidney, brain, and lungs (15,17,23). It was noted that the regulatory effect of ET-1 on iNOS seemed more prominent in protein expressions in the cirrhotic liver upon LPS stimulation whereas the effect was minimal in the sham-operated liver (Fig.…”

Section: Discussionmentioning

confidence: 81%

Inhibition of Endothelin-1-Mediated Up-Regulation of Inos by Bosentan Ameliorates Endotoxin-Induced Liver Injury in Cirrhosis

Keller¹,

Karaa²,

Paxian³

et al. 2006

Shock

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Endothelin-1 (ET-1) has been shown to regulate the expression of various genes in addition to its vasoconstrictor role in the liver. Elevated levels of ET-1 during cirrhosis play an important role in the observed microcirculatory dysfunction; however, its role as a transcription regulator remains unclear. This study aimed to determine the role of ET-1 in the hepatic gene expression of vasomediators after cirrhosis in response to LPS. Cirrhosis was induced by bile duct ligation (BDL) for 1 or 3 weeks in male Sprague-Dawley rats. Following 1 or 3 weeks of BDL or sham operation (sham), rats received an intravenous (i.v.) injection of bosentan, a dual-selective ETA/B receptor antagonist (30 mg/kg bw) or saline, and an intraperitoneal (i.p.) injection of LPS (1 mg/kg bw). Plasma alanine aminotransferase (ALT) levels were significantly elevated in 1- and 3-week BDL animals. Six hours following LPS, the elevated ALT levels were markedly exacerbated in 3-week BDL animals, which were significantly ameliorated with bosentan treatment. LPS resulted in increased ET-1, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2 mRNA expressions in both sham and BDL rats. Bosentan significantly inhibited the up-regulations of ET-1, iNOS, and COX-2 mRNA. Our data strongly suggest that ET-1 plays an important role in up-regulating the expression of iNOS, COX-2, and ET-1 itself in hepatic tissue following LPS challenge, which may contribute to the observed hepatocellular injury during endotoxemia in cirrhosis. Thus, due to significant increases in ET-1 levels during cirrhosis, ET-1 receptor blockade may prove to be of great therapeutic value in the treatment of cirrhotic patients exposed to secondary injuries such as endotoxemia.

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Section: Discussionmentioning

confidence: 81%

Inhibition of Endothelin-1-Mediated Up-Regulation of Inos by Bosentan Ameliorates Endotoxin-Induced Liver Injury in Cirrhosis

Keller¹,

Karaa²,

Paxian³

et al. 2006

Shock

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“…This effect could be mediated through endothelin activation, as iNOS stimulation by endothelin has been observed in other cell types such as chondrocytes and primary glial cells. [33][34][35][36] The NO effect is transferable through endothelially conditioned medium. Conditioned media from pressurized ECs exerts growth-inhibitory effects on recipient SMCs compared to the effects of media from control ECs.…”

Section: Discussionmentioning

confidence: 99%

Ambient pressure upregulates nitric oxide synthase in a phosphorylated-extracellular regulated kinase– and protein kinase C–dependent manner

Vouyouka

Jiang

Rastogi

et al. 2006

Journal of Vascular Surgery

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Intimal hyperplasia is the main cause for restenosis that complicates 10% to 30% of all such vascular procedures and 30% to 40% of endovascular procedures. This article provides some novel information about smooth muscle cell/endothelial cell interaction, one of the main regulators of vascular remodeling and intimal hyperplasia. The role of endothelial cell/smooth muscle cell interaction cannot be studied well in vivo because these interactions cannot be distinguished from other factors that coexist in vivo, such as flow dynamics, matrix proteins, inflammatory factors, and interactions with other cells in the vascular wall and in the bloodstream. In this work, we use pressure as a triggering stimulus to alter in vitro endothelial behavior and identify important changes in endothelial regulation of smooth muscle cell biology. The pathways involved in this process and discussed in this article could ultimately be used to manipulate endothelial cell/smooth muscle cell interaction in clinical disease.

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“…In various cell types (HUVEC, monocytes, Kupffer and ciliary epithelial cells), ET‐1 is also able to induce iNOS expression (Stephenson et al ., 1997; Schena et al ., 1999; Prasanna et al ., 2000). Furthermore, the induction of iNOS, by TNF α or other cytokines, could be positively or negatively regulated by ET‐1 (glial, vascular smooth muscle or mesangial cells, Beck et al ., 1995; Hirahashi et al ., 1996; Ikeda et al ., 1997; Oda et al ., 1997; Murayama et al ., 1998). However, in adipocytes, the effect of ET‐1 on iNOS expression remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Endothelin‐1 inhibits TNFα‐induced iNOS expression in 3T3‐F442A adipocytes

Mérial-Kieny

Lonchampt

Cogé

et al. 2003

British J Pharmacology

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1 Endothelin-1 (ET-1) and tumor necrosis factor a (TNFa) by their action on adipocytes have been independently linked to the pathogenesis of insulino-resistance. In isolated adipocytes, TNFa induces the expression of the inducible nitric oxide synthase (iNOS). The purpose of the present work was, in the 3T3-F442A adipocyte cell line, to characterise TNFa-induced iNOS expression and to determine whether or not ET-1 could influence TNFa-induced iNOS expression and NO production. 2 In differentiated 3T3-F442A, treatment with TNFa (20 ng ml À1) induced the expression of a functional iNOS as demonstrated by nitrite assay, Western blot, reverse transcription -polymerase chain reaction and Northern blot analysis. TNFa-induced iNOS expression requires nuclear factor kB activation, but does not necessitate the activation of the PI-3 kinase/Akt and P38 -MAP kinase pathways. 3 ET-1, but not ET-3, inhibited the TNFa-induced expression of iNOS protein and mRNA as well as nitrite production. The effects of ET-1 were blocked by a specific ETA (BQ123, pA 2 7.4) but not by a specific ETB receptor antagonist (BQ788). 3T3-F442A adipocytes express the mRNAs for prepro-ET-1 and the ET-A receptor subtype, but not for the ET-B subtype. 4 The inhibitory effect of ET-1 was not affected by bisindolylmaleimide, SB 203580 or indomethacin, inhibitors of protein kinase C, p38-MAP kinase and cyclooxygenase, respectively, and was not associated with cAMP production. However, the effect of ET-1 was partially reversed by wortmannin, suggesting the involvement of PI3 kinase in the transduction signal of ET-1. 5 Differentiated 3T3-F442A adipocytes did not release ET-1 with or without exposure to TNFa, although the mRNA for preproET-1 was detected in both pre-and differentiated adipocytes. 6 Thus, these results confirm that adipocytes are a target for circulating ET-1 and demonstrate that the activation of the ETA receptor subtype can prevent TNFa-induced iNOS expression.

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Regulation of inducible no synthase expression by endothelin in primary cultured glial cells

Cited by 9 publications

References 14 publications

Inhibition of Endothelin-1-Mediated Up-Regulation of Inos by Bosentan Ameliorates Endotoxin-Induced Liver Injury in Cirrhosis

Inhibition of Endothelin-1-Mediated Up-Regulation of Inos by Bosentan Ameliorates Endotoxin-Induced Liver Injury in Cirrhosis

Ambient pressure upregulates nitric oxide synthase in a phosphorylated-extracellular regulated kinase– and protein kinase C–dependent manner

Endothelin‐1 inhibits TNFα‐induced iNOS expression in 3T3‐F442A adipocytes

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