Over-expression of caveolin-1 aggravate LPS-induced inflammatory response in AT-1 cells via up-regulation of cPLA2/p38 MAPK

Lv, Xuejun; Li, Yuying; Zhang, Yong-Juan; Mao, Mingzhi; Qian, Guisheng

doi:10.1007/s00011-010-0157-9

Cited by 23 publications

(21 citation statements)

References 56 publications

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“…Cav-1 −/− mice challenged with LPS showed attenuation of immune cell infiltration, microvascular leakage, and edema and had reduced LPS-induced mortality compared to controls. In lung alveolar cells, overexpression of Cav-1 aggravated LPS injury and increased the production of the TLR4-induced, pro-inflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα) providing positive evidence that Cav-1 promotes TLR4 signaling (Lv et al, 2010). Two non-exclusive mechanisms have been proposed to describe how Cav-1 promotes TLR4 signaling in pulmonary inflammation: (1) an indirect, nitric oxide-dependent mechanism whereby eNOS hyper-activity secondary to loss Cav-1 induces nitration of TLR4 signaling components and suppression of downstream signaling (Mirza et al, 2010); (2) a direct effect whereby tyrosine phosphorylated Cav-1 interacts with TLR4 and promotes the assembly of the TLR4-MyD88 signaling complex (Jiao et al, 2013).…”

Section: Caveolins/caveolae In the Neuroretina And Rpementioning

confidence: 99%

Caveolins and caveolae in ocular physiology and pathophysiology

Reagan

McClellan

et al. 2017

Progress in Retinal and Eye Research

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Caveolae are specialized, invaginated plasma membrane domains that are defined morphologically and by the expression of signature proteins called, caveolins. Caveolae and caveolins are abundant in a variety of cell types including vascular endothelium, glia, and fibroblasts where they play critical roles in transcellular transport, endocytosis, mechanotransduction, cell proliferation, membrane lipid homeostasis, and signal transduction. Given these critical cellular functions, it is surprising that ablation of the caveolae organelle does not result in lethality suggesting instead that caveolae and caveolins play modulatory roles in cellular homeostasis. Caveolar components are also expressed in ocular cell types including retinal vascular cells, Müller glia, retinal pigment epithelium (RPE), conventional aqueous humor outflow cells, the corneal epithelium and endothelium, and the lens epithelium. In the eye, studies of caveolae and other membrane microdomains (i.e., “lipid rafts”) have lagged behind what is a substantial body of literature outside vision science. However, interest in caveolae and their molecular components has increased with accumulating evidence of important roles in vision-related functions such as blood-retinal barrier homeostasis, ocular inflammatory signalling, pathogen entry at the ocular surface, and aqueous humor drainage. The recent association of CAV1/2 gene loci with primary open angle glaucoma and intraocular pressure has further enhanced the need to better understand caveolar functions in the context of ocular physiology and disease. Herein, we provide the first comprehensive review of literature on caveolae, caveolins, and other membrane domains in the context of visual system function. This review highlights the importance of caveolae domains and their components in ocular physiology and pathophysiology and emphasizes the need to better understand these important modulators of cellular function.

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Section: Caveolins/caveolae In the Neuroretina And Rpementioning

confidence: 99%

Caveolins and caveolae in ocular physiology and pathophysiology

Reagan

McClellan

et al. 2017

Progress in Retinal and Eye Research

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“…These results further confirmed the previous studies by Garrean et al (28), which showed that cav-1 Ϫ/Ϫ mice have a reduced inflammatory response following LPS via NF-B-mediated pathways. Lv et al (61) observed that overexpression of cav-1 aggravates LPS-induced inflammation in that mouse lung alveolar type 1 cells had increased inflammatory cytokine production including IL-6 and TNF␣. Instead of using cav-1 Ϫ/Ϫ , the "gain of function" approach used in this study further endorsed the hypothesis that cav-1 mediates LPS-induced inflammation during lung injury (61,70).…”

Section: Caveolin-1 and Lung Injurymentioning

confidence: 99%

“…Lv et al (61) observed that overexpression of cav-1 aggravates LPS-induced inflammation in that mouse lung alveolar type 1 cells had increased inflammatory cytokine production including IL-6 and TNF␣. Instead of using cav-1 Ϫ/Ϫ , the "gain of function" approach used in this study further endorsed the hypothesis that cav-1 mediates LPS-induced inflammation during lung injury (61,70). Similarly, Wang and coworkers (109) first observed cav-1 expression in murine alveolar macrophages and showed that cav-1 in murine alveolar and peritoneal macrophages regulated LPSinduced proinflammatory TNF␣ and IL-6 cytokine production.…”

Section: Caveolin-1 and Lung Injurymentioning

confidence: 99%

Caveolin-1: a critical regulator of lung injury

Jin

Lee

Minshall

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

103

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Caveolin-1 (cav-1), a 22-kDa transmembrane scaffolding protein, is the principal structural component of caveolae. Cav-1 regulates critical cell functions including proliferation, apoptosis, cell differentiation, and transcytosis via diverse signaling pathways. Abundant in almost every cell type in the lung, including type I epithelial cells, endothelial cells, smooth muscle cells, fibroblasts, macrophages, and neutrophils, cav-1 plays a crucial role in the pathogenesis of acute lung injury (ALI). ALI and its severe form, acute respiratory distress syndrome (ARDS), are responsible for significant morbidity and mortality in intensive care units, despite improvement in ventilation strategies. The pathogenesis of ARDS is still poorly understood, and therapeutic options remain limited. In this article, we summarize recent data regarding the regulation and function of cav-1 in lung biology and pathology, in particular as it relates to ALI. We further discuss the potential molecular and cellular mechanisms by which cav-1 expression contributes to ALI. Investigating the cellular functions of cav-1 may provide new insights for understanding the pathogenesis of ALI and provide novel targets for therapeutic interventions in the future.

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“…Altered expression of Cav-1 has been implicated in the pathogenesis of several lung diseases (14). Cav Ϫ/Ϫ mice have thickened alveolar walls and irregular alveolar spaces with increased deposition of extracellular matrix and TGF-␤ activity, whereas overexpression of Cav-1 aggravates lipopolysaccharide (LPS)-induced inflammation and subsequent lung injury (17,29).…”

mentioning

confidence: 99%

Antenatal glucocorticoids counteract LPS changes in TGF-β pathway and caveolin-1 in ovine fetal lung

Collins

Kunzmann

Kuypers

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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Inflammation and antenatal glucocorticoids, the latter given to mothers at risk for preterm birth, affect lung development and may contribute to the development of bronchopulmonary dysplasia (BPD). The effects of the combined exposures on inflammation and antenatal glucocorticoids on transforming growth factor (TGF)-β signaling are unknown. TGF-β and its downstream mediators are implicated in the etiology of BPD. Therefore, we asked whether glucocorticoids altered intra-amniotic lipopolysaccharide (LPS) effects on TGF-β expression, its signaling molecule phosphorylated sma and mothers against decapentaplegic homolog 2 (pSmad2), and the downstream mediators connective tissue growth factor (CTGF) and caveolin-1 (Cav-1). Ovine singleton fetuses were randomized to receive either an intra-amniotic injection of LPS and/or maternal betamethasone (BTM) intramuscularly 7 and/or 14 days before delivery at 120 days gestational age (GA; term = 150 days GA). Saline was used for controls. Protein levels of TGF-β1 and -β2 were measured by ELISA. Smad2 phosphorylation was assessed by immunohistochemistry and Western blot. CTGF and Cav-1 mRNA and protein levels were determined by RT-PCR and Western blot. Free TGF-β1 and -β2 and total TGF-β1 levels were unchanged after LPS and/or BTM exposure, although total TGF-β2 increased in animals exposed to BTM 7 days before LPS. pSmad2 immunostaining increased 7 days after LPS exposure although pSmad2 protein expression did not increase. Similarly, CTGF mRNA and protein levels increased 7 days after LPS exposure as Cav-1 mRNA and protein levels decreased. BTM exposure before LPS prevented CTGF induction and Cav-1 downregulation. This study demonstrated that the intrauterine inflammation-induced TGF-β signaling can be inhibited by antenatal glucocorticoids in fetal lungs.

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Over-expression of caveolin-1 aggravate LPS-induced inflammatory response in AT-1 cells via up-regulation of cPLA2/p38 MAPK

Abstract: Our data demonstrated that over-expression of caveolin-1 aggravates the AT-1 injury induced by LPS, involving in modulation of the cPLA2 mediated by the cPLA2/p38 MAPK pathway.

Cited by 23 publications

References 56 publications

Caveolins and caveolae in ocular physiology and pathophysiology

Caveolins and caveolae in ocular physiology and pathophysiology

Caveolin-1: a critical regulator of lung injury

Antenatal glucocorticoids counteract LPS changes in TGF-β pathway and caveolin-1 in ovine fetal lung

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