IL-1 beta inhibits ET-1 production by ATII cells in vitro: evidence for involvement of cyclooxygenase 2 pathway

Odoux, Christine; Crestani, Bruno; Lebrun, Gaëlle; Rolland, Corinne; Aubin, Perrine; Fournier, Thierry; Fiet, Jean; Aubier, Michel

doi:10.1152/ajplung.1997.273.1.l193

Cited by 5 publications

(3 citation statements)

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“…In addition, the inhibitory effects of IL-1␤ were reversed when COX-2 activity was blocked using either indomethacin or DFU. Our results using primary human pulmonary smooth muscle cells are supported by one other study in the literature in which IL-1␤ inhibited ET-1 release by alveolar epithelial cells (Odoux et al, 1997) via a COXdependent pathway. Moreover, in the only clinical study to our knowledge to address the effect of COX inhibition on pulmonary hemodynamics in patients with pulmonary hypertension, administration of indomethacin resulted in increased pulmonary vascular resistance (Hermiller et al, 1982).…”

Section: Discussionsupporting

confidence: 88%

Cyclooxygenase-2 Acts as an Endogenous Brake on Endothelin-1 Release by Human Pulmonary Artery Smooth Muscle Cells: Implications for Pulmonary Hypertension

et al. 2002

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Endothelin-1 is a potent vasoconstrictor and comitogen for vascular smooth muscle. As such, it has been implicated in pulmonary vascular remodeling and in the development of pulmonary hypertension. Prostacyclin has been shown to be an effective therapy for human pulmonary hypertension, reducing morbidity and mortality, although the mechanism of its action is unknown. Here, we show that the combination of TNF-␣ and IFN-␥ induces the release of endothelin-1 from human pulmonary artery smooth muscle cells via increased transcription of prepro endothelin-1. The release of endothelin-1 and the transcription of prepro endothelin-1 mRNA were inhibited by the activity of coinduced cyclooxygenase-2. Endothelin-1 release was also inhibited by a prostacyclin-mimetic (cicaprost). Thus, under inflammatory conditions, in which vascular smooth muscle is an important source of endothelin-1, the induction of cyclooxygenase-2 represents an endogenous "braking" mechanism. In addition, the beneficial effects of prostacyclin in the treatment of pulmonary hypertension may be caused, at least in part, by the inhibition of endothelin-1 release. Finally, we suggest that these observations may help to explain why patients with pulmonary hypertension experience exacerbations after taking indomethacin and that the newly introduced selective cyclooxygenase-2 inhibitors may increase endothelin-1 production in susceptible patients, leading to vascular remodeling and the development of pulmonary hypertension.In healthy subjects, pulmonary vascular tone and remodeling is controlled by the balanced, local release of vasoactive mediators, which are chiefly produced by the endothelium, and they act on the underlying smooth muscle. These mediators include the vasodilators nitric oxide and prostacyclin (PGI 2 ) and the vasoconstrictor endothelin-1 (ET-1). Under inflammatory conditions, these control mechanisms are lost, leading to pulmonary vascular dysfunction, characterized by vasoconstriction and proliferation of vascular smooth muscle (Wort and Evans, 1999). Clinically, this leads to the development of increased pulmonary vascular resistance and the development of pulmonary hypertension. ET-1, a 21-amino acid peptide, is formed from big-ET-1 by the action of membrane-bound metalloproteases termed "endothelin-converting enzymes" (ECEs) (Schmidt et al

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Section: Discussionsupporting

confidence: 88%

Cyclooxygenase-2 Acts as an Endogenous Brake on Endothelin-1 Release by Human Pulmonary Artery Smooth Muscle Cells: Implications for Pulmonary Hypertension

et al. 2002

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“…Rat ATII cells in primary culture [7], and a cell line derived from rat ATII cells, have been shown to secrete ET-1 in vitro [8].…”

Section: Hypoxia Reduces Endothelin Production By Rat Alveolar Type Imentioning

confidence: 99%

“…Rat preproET-1 mRNA and glyceraldehyde-phosphate dehydrogenase (GAPDH) mRNA were detected by a Northern blot analysis and quantified through an electronic autoradiography device (Instant Imager®; Packard, Groningen, the Netherlands) as described previously [7]. The ratio of the preproET-1 mRNA signal and the corresponding GAPDH mRNA signal was calculated for each sample.…”

Section: Northern Blot Analysismentioning

confidence: 99%

Hypoxia reduces endothelin production by rat alveolar type II cells in primary culture

Crestani

Odoux²,

Rolland³

et al. 1998

Eur Respir J

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Type II alveolar epithelial cells (ATII cells) have been shown to play a key role in the regulation of the alveolar space. ATII cells synthesize and secrete surfactant, control the volume and composition of the epithelial lining fluid and proliferate and differentiate into type I alveolar epithelial cells after injury in order to maintain the integrity of the alveolar wall. Moreover, ATII cells are ideally located to have a role in modulating the activation or proliferation state of macrophages, fibroblasts or endothelial cells, because of the close proximity of the cell types in the alveolar space.The interactions between the alveolar epithelial cells and the other cells located in the alveoli are brought about by the secretion of mediators such as cytokines [1], but other mediators are probably involved in this phenomenon. Among these mediators, endothelin (ET)-1 a 21 amino acid peptide may play an important role. Indeed, beside its potent effect on the constriction of vascular and bronchial smooth muscle cells, ET-1 acts as a mitogen for different cell types, such as fibroblasts or smooth muscle cells [2]. ET-1 is also involved in the modulation of the inflammatory response through a direct effect on alveolar macrophages [3] or mastocytes [4].It has been shown that hyperplastic alveolar epithelial cells express preproendothelin-1 (preproET-1) messenger ribonucleic acid (mRNA) and immunoreactive ET (irET)-1 in the human fibrotic lung [5], although conflicting data exist [6]. Rat ATII cells in primary culture [7], and a cell line derived from rat ATII cells, have been shown to secrete ET-1 in vitro [8].Hypoxia has been identified as an important modulator of ET-1 production by endothelial cells. Hypoxia increases ET-1 production by human umbilical vein endothelial cells [9], but decreases ET-1 production by rat lung endothelial cells [10]. The effect of hypoxia on ET-1 production by rat ATII cells has never been evaluated, despite the fact that ATII cells are potential targets for hypoxia in the alveolar space both in physiological (high altitude) and pathological (e.g. lung parenchyma consolidation) conditions. Therefore, the aims of this study were: 1) to characterize the regulation of ET-1 production by rat ATII cells in primary culture under low oxygen tension; and 2) to evaluate the influence of nitric oxide on ET-1 production by rat ATII cells. Materials and methods ReagentsTissue culture media and foetal bovine serum were obtained from Gibco BRL Life Technologies (Cergy Pontoise, Hypoxia reduces endothelin production by rat alveolar type II cells in primary culture. B. Crestani, C. Odoux, C. Rolland, F. Moldovan, P. Cornillet, J. Fiet, M. Aubier. ©ERS Journals Ltd 1998. ABSTRACT: The purpose of the study was to describe endothelin (ET) production and to characterize the effect of hypoxia on preproendothelin-1 (preproET-1) messenger ribonucleic acid (mRNA) expression and ET secretion by rat type II pneumocytes in vitro.Rat type II pneumocytes were incubated in a sealed chamber containing a normoxic (21% ...

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Granulocyte–macrophage colony-stimulating factor and interleukin-3 potentiate interferon-γ-mediated endothelin production by human monocytes: role of protein kinase C

Salh

Hoeflick²,

Kwan³

et al. 1998

Immunology

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Monocytic cells have been shown to produce endothelin, a potent vasoconstrictor molecule with immune modulating properties. The signalling mechanisms involved in this response are presently unclear. Monocytes are also believed to play an important role in inflammatory bowel disease (IBD). The objective of this study was to characterize the role of various cytokines, bacterial lipopolysaccharide (LPS) and colony-stimulating factors on the production of endothelin (ET) by freshly isolated human monocytes. Compelling circumstantial evidence exists for the conditions being investigated occurring in inflamed bowel mucosa to where monocytes migrate. Whereas LPS stimulated the release of 7 pg ET/2x106 cells in 40 hr, interferon-gamma (IFN-gamma) stimulated 45 pg ET/2x106 cells in 40 hr. There was an additive response when the two stimuli were employed together. Significantly the addition of either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3) effected a two- to threefold, dose-dependent increase in the production of ET. Production of endothelin was reproducibly blocked by the addition of the protein kinase C (PKC) inhibitors staurosporine and H7, as well as by the protein synthesis inhibitor cycloheximide. Assessment of the activities of the alpha and beta isoforms of conventional protein kinase C (PKC), as determined by MonoQ column fractionated calcium and lipid activatible phosphotransferase activity towards myelin basic protein (MBP) revealed an additive effect of using LPS, IFN-gamma and GM-CSF, which was even greater than that demonstrated for phorbol myristate acetate (PMA). Additionally the secretion of ET by monocytes from Crohn's disease patients (in remission) was analysed and compared with an age-matched control group. There was no significant difference between the two. These results: (1) demonstrate an important synergistic role for GM-CSF and IL-3 in the predominantly IFN-gamma-mediated ET production by normal human monocytes; (2) indicate a possible role for the protein kinase C signalling pathway in this response; and (3) argue against a primary abnormality of ET production in peripheral monocytes from patients with Crohn's disease.

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IL-1 beta inhibits ET-1 production by ATII cells in vitro: evidence for involvement of cyclooxygenase 2 pathway

Cited by 5 publications

References 0 publications

Cyclooxygenase-2 Acts as an Endogenous Brake on Endothelin-1 Release by Human Pulmonary Artery Smooth Muscle Cells: Implications for Pulmonary Hypertension

Cyclooxygenase-2 Acts as an Endogenous Brake on Endothelin-1 Release by Human Pulmonary Artery Smooth Muscle Cells: Implications for Pulmonary Hypertension

Hypoxia reduces endothelin production by rat alveolar type II cells in primary culture

Granulocyte–macrophage colony-stimulating factor and interleukin-3 potentiate interferon-γ-mediated endothelin production by human monocytes: role of protein kinase C

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