TNF-α-Induced cPLA2 Expression via NADPH Oxidase/Reactive Oxygen Species-Dependent NF-κB Cascade on Human Pulmonary Alveolar Epithelial Cells

Lin, Chih‐Chung; Lin, Wei‐Ning; Cho, Rou-Ling; Wang, Chenyu; Hsiao, Li-Der; Yang, Che‐Hua

doi:10.3389/fphar.2016.00447

Cited by 22 publications

(25 citation statements)

References 57 publications

(91 reference statements)

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“…It was found that the activation of NADPH oxidase in alveolar epithelial cells is a source of ROS production [42]. Inhibition of NADPH oxidase by apocynin or diphenyleneiodonium chloride reversed TNF-α-mediated cPLA2α expression [43]. Here, we found that the stimulation of leptin promoted p47 phox phosphorylation and ROS production in an OB-R-dependent manner.…”

Section: Discussionsupporting

confidence: 57%

Participation of NADPH Oxidase-Related Reactive Oxygen Species in Leptin-Promoted Pulmonary Inflammation: Regulation of cPLA2α and COX-2 Expression

Hsu¹,

Lin

Chang

et al. 2019

IJMS

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Obesity is a worldwide epidemic problem and correlates to varieties of acute or chronic lung diseases such as acute respiratory distress syndrome, chronic obstructive pulmonary disease, and pulmonary fibrosis. An increase of leptin, a kind of adipokine, in lean mice plasma has been found to impair immune responses and facilitate the infection of Klebsiella pneumoniae, resulting in increased pneumonia severity. Also, a higher leptin level is found in exhaled breath condensates of obese or asthmatic subjects, compared to healthy ones, suggesting that leptin is involved in the occurrence or exacerbation of lung injury. In previous studies, we showed that leptin stimulated cytosolic phospholipase A2-α (cPLA2α) gene expression in lung alveolar type II cells via mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB)-activated coactivator p300. Herein, we show that the in vivo application of leptin in the respiratory system upregulated the expression of inflammatory proteins cPLA2α and cyclooxygenase-2 (COX-2) together with leukocyte infiltration. Treatment with an ROS scavenger (N-acetylcysteine, NAC), an NADPH oxidase inhibitor (apocynin), or an activating protein (AP)-1 inhibitor (tanshinone IIA) attenuated leptin-mediated cPLA2α/COX-2 expression and leukocyte recruitment in the lung. Leptin increased intracellular oxidative stress in a leptin receptor (OB-R) and NADPH oxidase-dependent manner, leading to the phosphorylation of the AP-1 subunit c-Jun. In summation, leptin increased lung cPLA2α/COX-2 expression and leukocyte recruitment via the NADPH oxidase/ROS/AP-1 pathway. Understanding the inflammatory effects of leptin on the pulmonary system provides opportunities to develop strategies against lung injury related to metabolic syndrome or obesity.

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Section: Discussionsupporting

confidence: 57%

Participation of NADPH Oxidase-Related Reactive Oxygen Species in Leptin-Promoted Pulmonary Inflammation: Regulation of cPLA2α and COX-2 Expression

Hsu¹,

Lin

Chang

et al. 2019

IJMS

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“…NADPH oxidase (NOX) activity was measured using lucigenin as described elsewhere [ 13 ]. Briefly, the coculture cells or the activated HSCs were harvested after culturing for 24, 48, or 76 hours and centrifuged at 400 ×g for 10 min at 4°C, and the cell pellet was kept on ice after resuspended by 35 μ l/per well of the ice-cold RPMI-1640 medium.…”

Section: Methodsmentioning

confidence: 99%

NADPH Oxidase Signaling Pathway Mediates Mesenchymal Stem Cell-Induced Inhibition of Hepatic Stellate Cell Activation

Qiao

Zhou

Qin

et al. 2018

Stem Cells International

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Background Bone marrow-derived mesenchymal stem cells (BMSCs) have blossomed into an effective approach with great potential for the treatment of liver fibrosis. The aim of this study was to investigate the underlying antifibrosis mechanisms by which the BMSC inhibit activated hepatic stellate cells (HSCs) in vivo and in vitro. Methods To study the effect of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) on activated HSCs, we used HSCs and the coculture systems to evaluate the inhibition of activated HSCs from the aspects of the apoptosis of activated HSCs. In addition, activation of NADPH oxidase pathway and the changes in liver histopathology were tested by using the carbon tetrachloride- (CCl4-) induced liver fibrosis in mice. Results Introduction of hBM-MSCs significantly inhibited the proliferation of activated HSCs by inducing the apoptosis process of activated HSCs. The effect of hBM-MSCs reduced the signaling pathway of NADPH oxidase in activated HSCs. Besides, the signaling pathway of NADPH oxidase mediated hBM-MSC upregulation of the expression of the peroxisome proliferator-activated receptor γ and downregulation of the expression of α1(I) collagen and alpha-smooth muscle actin (α-SMA) in activated HSCs. Moreover, the hBM-MSC-induced decrease in the signaling pathway of NADPH oxidase was accompanied by the decrease of the activated HSC number and liver fibrosis in a mouse model of CCl4-induced liver fibrosis. Conclusion The hBM-MSCs act as a promising drug source against liver fibrosis development with respect to hepatopathy as a therapeutic target.

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“…Due to the important role that PGES-1 plays in producing high levels of PGE-2, developing novel drug inhibitors of this enzyme is now an important pharmaceutical research focus [92,93]. Finally, both the expression of the phospholipase A2 gene as well as the activity of the enzyme can be increased dramatically by UVB [94,95], by NADH oxidase pathways [96], by MAPK and NF-kB pathways activated by IL-beta, TNF-alpha, and EGF receptors [97], and by cAMP signaling pathways [94,95,98,99].…”

Section: Regulation Of Pge-2 Production In Skinmentioning

confidence: 99%

“…Exposure of keratinocytes, fibroblasts or immune cells to such stimuli as UVB radiation, IL-1, ROS, or Lipopolysaccharide (LPS) can result in increased COX-2 gene expression, as well as increased activity of the genes for PGES and PLA2 [83,95]. By blocking the signaling pathway that leads to activation of transcription factors, particularly NF-kB that regulates these genes, natural anti-inflammatory compounds can block not only COX-2 expression, but expression of PGES [83] and/or cPLA2 [96,189]. A few examples of some natural compounds that block PGE-2 production, as well as other inflammatory mediators, are discussed below:…”

Section: 83mentioning

confidence: 99%

Role of PGE-2 and Other Inflammatory Mediators in Skin Aging and Their Inhibition by Topical Natural Anti-Inflammatories

Fuller

2019

Cosmetics

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Human skin aging is due to two types of aging processes, “intrinsic” (chronological) aging and “extrinsic” (external factor mediated) aging. While inflammatory events, triggered mainly by sun exposure, but also by pollutants, smoking and stress, are the principle cause of rapid extrinsic aging, inflammation also plays a key role in intrinsic aging. Inflammatory events in the skin lead to a reduction in collagen gene activity but an increase in activity of the genes for matrix metalloproteinases. Inflammation also alters proliferation rates of cells in all skin layers, causes thinning of the epidermis, a flattening of the dermo-epidermal junction, an increase in irregular pigment production, and, finally, an increased incidence of skin cancer. While a large number of inflammatory mediators, including IL-1, TNF-alpha and PGE-2, are responsible for many of these damaging effects, this review will focus primarily on the role of PGE-2 in aging. Levels of this hormone-like mediator increase quickly when skin is exposed to ultraviolet radiation (UVR), causing changes in genes needed for normal skin structure and function. Further, PGE-2 levels in the skin gradually increase with age, regardless of whether or not the skin is protected from UVR, and this smoldering inflammation causes continuous damage to the dermal matrix. Finally, and perhaps most importantly, PGE-2 is strongly linked to skin cancer. This review will focus on: (1) the role of inflammation, and particularly the role of PGE-2, in accelerating skin aging, and (2) current research on natural compounds that inhibit PGE-2 production and how these can be developed into topical products to retard or even reverse the aging process, and to prevent skin cancer.

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TNF-α-Induced cPLA2 Expression via NADPH Oxidase/Reactive Oxygen Species-Dependent NF-κB Cascade on Human Pulmonary Alveolar Epithelial Cells

Cited by 22 publications

References 57 publications

Participation of NADPH Oxidase-Related Reactive Oxygen Species in Leptin-Promoted Pulmonary Inflammation: Regulation of cPLA2α and COX-2 Expression

Participation of NADPH Oxidase-Related Reactive Oxygen Species in Leptin-Promoted Pulmonary Inflammation: Regulation of cPLA2α and COX-2 Expression

NADPH Oxidase Signaling Pathway Mediates Mesenchymal Stem Cell-Induced Inhibition of Hepatic Stellate Cell Activation

Role of PGE-2 and Other Inflammatory Mediators in Skin Aging and Their Inhibition by Topical Natural Anti-Inflammatories

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