Autocrine Function of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 in Proliferation of Human and Rat Pulmonary Artery Smooth-Muscle Cells

Jourdan, Karen B.; Evans, Timothy W.; Lamb, Nick; Goldstraw, Peter; Mitchell, Jane A.

doi:10.1165/ajrcmb.21.1.3502

Cited by 25 publications

(18 citation statements)

References 31 publications

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“…In cultured vascular smooth muscle cells, it has been reported that IL-1 possesses anti-proliferative effects through the induction of COX-2/iNOS (14). Furthermore, Libby et al (20) observed that IL-1␤ was able to induce vascular smooth muscle proliferation when the cells were treated with COX-2 inhibitor.…”

Section: Discussionmentioning

confidence: 99%

IL-1β inhibits intestinal smooth muscle proliferation in an organ culture system: involvement of COX-2 and iNOS induction in muscularis resident macrophages

Hori¹,

Momotani²,

Elorza³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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Ohama T, Hori M, Momotani E, Elorza M, Gerthoffer WT, Ozaki H. IL-1␤ inhibits intestinal smooth muscle proliferation in an organ culture system: involvement of COX-2 and iNOS induction in muscularis resident macrophages. Am J Physiol Gastrointest Liver Physiol 292: G1315-G1322, 2007. First published January 18, 2007 doi:10.1152/ajpgi.00487.2006.-Intestinal inflammation causes hyperplasia of smooth muscle that leads to thickening of the smooth muscle layer, resulting in dysmotility. IL-1␤ is a proinflammatory cytokine that plays a central role in intestinal inflammation. In this study, to evaluate the effect of IL-1␤ on proliferation of ileal smooth muscle cells in vivo, we utilized an organ culture system. When rat ileal smooth muscle tissue was cultured under serum-free conditions for 3 days, most smooth muscle cells maintained their arrangement and kept their contractile phenotype. When 10% FBS was added, an increased number of smooth muscle cells per unit area was observed. Moreover, immunohistochemical staining for PCNA demonstrated that FBS induced proliferation of smooth muscle cells. IL-1␤ inhibited the proliferative effect of FBS. Furthermore, IL-1␤ upregulated inducible nitric oxide (NO) synthase and cyclooxygenase-2 mRNA and protein and thus stimulated NO and PGE 2 productions. Moreover, exogenously applied NO and PGE 2 inhibited the increase of bromodeoxyuridine-positive cells stimulated with FBS. Immunostaining revealed that the majority of cyclooxygenase-2 and inducible NO synthase was located in the dense network of macrophages resident in the muscularis, which were immunoreactive to ED2. Based on these findings, IL-1␤ acts as an anti-proliferative mediator, which acts indirectly through the production of PGE 2 and NO from resident macrophage within ileal smooth muscle tissue.

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Section: Discussionmentioning

confidence: 99%

IL-1β inhibits intestinal smooth muscle proliferation in an organ culture system: involvement of COX-2 and iNOS induction in muscularis resident macrophages

Hori¹,

Momotani²,

Elorza³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Basal levels of nitrite produced by the explants may result from the induction of iNOS by the injury of explantation, as observed after balloon catheter injury of the rat [28]and pig [29]carotid artery. Of interest, cultured rat SMCs increase production of NO after treatment with IL-1β [30, 31], whereas human SMC [30, 31, 32]and whole aorta in culture [33]show little or no stimulation. Prostaglandins also partially mediate the inhibition of migration by IL-1β based on sensitivity to indomethacin.…”

Section: Discussionmentioning

confidence: 99%

Blockade of Smooth Muscle Cell Migration and Proliferation in Baboon Aortic Explants by Interleukin-1β and Tumor Necrosis Factor-α Is Nitric Oxide-Dependent and Nitric Oxide-Independent

Kenagy

Clowes

2000

J Vasc Res

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Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα) are found in injured and atherosclerotic vessels and have been shown to influence smooth muscle cell (SMC) function in vitro. We have investigated the effects of IL-1β and TNFα on SMC migration and proliferation in baboon aortic explants, an in vitro model of arterial injury. Because platelet-derived growth factor (PDGF) is also present in the vessel wall, we have studied the interaction of PDGF with the cytokines. IL-1β and TNFα inhibited migration of SMCs and synthesis of DNA by SMCs. Cell death (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cells and total DNA) was not altered by the cytokines. The cytokines increased levels of nitrite in the medium and L-nitroarginine partly reversed the inhibitory effects of the cytokines indicating a role for nitric oxide in these inhibitory effects. Treatment with indomethacin partially reversed the inhibition of migration, but not DNA synthesis by IL-1β suggesting cyclooxygenase products play an inhibitory role in migration. PDGF-BB reversed the inhibitory effect of the cytokines on SMC migration, but not mitogenesis, without changing levels of nitrite in the medium. These data show that IL-1β and TNFα decrease primate SMC migration and proliferation in arterial tissue partly through production of NO, and that PDGF antagonizes the effect of the cytokines. IL-1β and TNFα may act directly to limit injury-induced intimal hyperplasia by decreasing SMC migration and proliferation.

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“…In addition to its vasodilatory properties, prostacyclin also inhibits SMC proliferation by activation of cell surface prostanoid receptors, leading to activation of G-protein-coupled receptors and increasing cAMP production (see Figure 1) (19). The antiproliferative effects of cAMP have been demonstrated in many different cell types (20)(21)(22). Prostacyclin has been studied extensively in PAH and remains a cornerstone for therapeutic management in patients with severe PAH.…”

Section: Prostacyclinmentioning

confidence: 99%

Molecular Mechanisms of Pulmonary Arterial Remodeling

Crosswhite

Sun

2014

Mol Med

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Pulmonary arterial hypertension (PAH) is characterized by a persistent elevation of pulmonary arterial pressure and pulmonary arterial remodeling with unknown etiology. Current therapeutics available for PAH are primarily directed at reducing the pulmonary blood pressure through their effects on the endothelium. It is well accepted that pulmonary arterial remodeling is primarily due to excessive pulmonary arterial smooth muscle cell (PASMC) proliferation that leads to narrowing or occlusion of the pulmonary vessels. Future effective therapeutics will be successful in reversing the vascular remodeling in the pulmonary arteries and arterioles. The purpose of this review is to provide updated information on molecular mechanisms involved in pulmonary arterial remodeling with a focus on growth factors, transcription factors, and epigenetic pathways in PASMC proliferation. In addition, this review will highlight novel therapeutic strategies for potentially reversing PASMC proliferation.

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Autocrine Function of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 in Proliferation of Human and Rat Pulmonary Artery Smooth-Muscle Cells

Cited by 25 publications

References 31 publications

IL-1β inhibits intestinal smooth muscle proliferation in an organ culture system: involvement of COX-2 and iNOS induction in muscularis resident macrophages

IL-1β inhibits intestinal smooth muscle proliferation in an organ culture system: involvement of COX-2 and iNOS induction in muscularis resident macrophages

Blockade of Smooth Muscle Cell Migration and Proliferation in Baboon Aortic Explants by Interleukin-1β and Tumor Necrosis Factor-α Is Nitric Oxide-Dependent and Nitric Oxide-Independent

Molecular Mechanisms of Pulmonary Arterial Remodeling

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