Phospholipase D1 Has a Pivotal Role in Interleukin-1β-Driven Chronic Autoimmune Arthritis through Regulation of NF-κB, Hypoxia-Inducible Factor 1α, and FoxO3a

Kang, Dong Woo; Park, Mi-Kyung; Oh, Hyeyoung; Lee, Dong Gun; Park, Sung-Hwan; Choi, Kang‐Yell; Cho, Mi‐La; Min, Do Sik

doi:10.1128/mcb.01519-12

Cited by 39 publications

(34 citation statements)

References 40 publications

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“…However, overexpression of PLD2, but not PLD1, increases LPS‐induced NO synthesis and iNOS expression, and knockdown of PLD2 using PLD2 siRNA completely abolishes iNOS expression and NO synthesis in RAW 264.7 cells, suggesting that LPS upregulates NO synthesis specifically through PLD2 28 . In contrast, PLD1 inhibition by a PLD1‐selective inhibitor (VU0155069) and PLD1 siRNA, but not PLD2, abolishes IL‐1β‐induced expression of proinflammatory mediators in synoviocytes, as well as joint inflammation and breakdown, in an arthritic animal model 24 . NO, PGE 2 , IL‐1β, TNF‐α, and IL‐8 are recognized as important cytokines in the pathogenesis and progression of periodontitis 45 .…”

Section: Discussionmentioning

confidence: 97%

Expression of Phospholipase D in Periodontitis and Its Role in the Inflammatory and Osteoclastic Response by Nicotine‐ and Lipopolysaccharide‐Stimulated Human Periodontal Ligament Cells

Shin

Kim

Lee

et al. 2015

Journal of Periodontology

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Section: Discussionmentioning

confidence: 97%

Expression of Phospholipase D in Periodontitis and Its Role in the Inflammatory and Osteoclastic Response by Nicotine‐ and Lipopolysaccharide‐Stimulated Human Periodontal Ligament Cells

Shin

Kim

Lee

et al. 2015

Journal of Periodontology

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“…It is interesting to note that both the HIF-1α and NF-κB pathways are regulated by inflammatory mediators, as well as by hypoxia (53,6,54). Inflammatory stimuli activate the HIF pathway through transcriptional upregulation of HIF-1 mRNA expression in an NF-κB-dependent manner (55).…”

Section: Discussionmentioning

confidence: 99%

Amelioration of hypoxia and LPS-induced intestinal epithelial barrier dysfunction by emodin through the suppression of the NF-κB and HIF-1α signaling pathways

et al. 2014

International Journal of Molecular Medicine

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Intestinal barrier dysfunction occurs in critical illnesses and involves the inflammatory and hypoxic injury of intestinal epithelial cells. Researchers are still defining the underlying mechanisms and evaluating therapeutic strategies for restoring intestinal barrier function. The anti-inflammatory drug, emodin, has been shown to exert a protective effect on intestinal barrier function; however, its mechanisms of action remain unknown. In this study, we investigated the protective effects of emodin on intestinal barrier function and the underlying mechanisms in intestinal epithelial cells challenged with lipopolysaccharide (LPS) and hypoxia/reoxygenation (HR). To induce barrier dysfunction, Caco-2 monolayers were subjected to HR with or without LPS treatment. Transepithelial electrical resistance and paracellular permeability were measured to evaluate barrier function. The expression of the tight junction (TJ) proteins, zonula occludens (ZO)-1, occludin, and claudin-1, as well as that of hypoxia-inducible factor (HIF)-1α, phospho-IκB-α, phospho-nuclear factor (NF)-κB p65 and cyclooxygenase (COX)-2 was determined by western blot analysis. The results revealed that emodin markedly attenuated the decrease in transepithelial electrical resistance and the increase in paracellular permeability in the Caco-2 monolayers treated with LPS and subjected to HR. Emodin also markedly alleviated the damage caused by LPS and HR (manifested by a decrease in the expression of the TJ protein, ZO-1), and inhibited the expression of HIF-1α, IκB-α, NF-κB and COX-2 in a dose-dependent manner. In conclusion, our data suggest that emodin attenuates LPS-and HR-induced intestinal epithelial barrier dysfunction by inhibiting the HIF-1α and NF-κB signaling pathways and preventing the damage caused to the TJ barrier (shown by the decrease in the expression of ZO-1).

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“…PLD1 modulates lipid signaling by catalyzing the hydrolysis of phosphatidylcholine into choline and the signaling molecule phosphatidic acid, which regulates multiple downstream pathways implicated in hypertension including cytoskeletal organization and inflammation30. PLD1 is upregulated in response to IL-1β stimulation in chronic autoimmune arthritis31 and PLD1 protein is regulated by RHOA32, which has an important role in hypertension pathophysiology33. Both PLD1 and RHOA mRNA were elevated in AAHT, but were unchanged in whites.…”

Section: Discussionmentioning

confidence: 99%

Racial differences in microRNA and gene expression in hypertensive women

Dluzen

Hooten

Zhang

et al. 2016

Sci Rep

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Systemic arterial hypertension is an important cause of cardiovascular disease morbidity and mortality. African Americans are disproportionately affected by hypertension, in fact the incidence, prevalence, and severity of hypertension is highest among African American (AA) women. Previous data suggests that differential gene expression influences individual susceptibility to selected diseases and we hypothesized that this phenomena may affect health disparities in hypertension. Transcriptional profiling of peripheral blood mononuclear cells from AA or white, normotensive or hypertensive females identified thousands of mRNAs differentially-expressed by race and/or hypertension. Predominant gene expression differences were observed in AA hypertensive females compared to AA normotensives or white hypertensives. Since microRNAs play important roles in regulating gene expression, we profiled global microRNA expression and observed differentially-expressed microRNAs by race and/or hypertension. We identified novel mRNA-microRNA pairs potentially involved in hypertension-related pathways and differently-expressed, including MCL1/miR-20a-5p, APOL3/miR-4763-5p, PLD1/miR-4717-3p, and PLD1/miR-4709-3p. We validated gene expression levels via RT-qPCR and microRNA target validation was performed in primary endothelial cells. Altogether, we identified significant gene expression differences between AA and white female hypertensives and pinpointed novel mRNA-microRNA pairs differentially-expressed by hypertension and race. These differences may contribute to the known disparities in hypertension and may be potential targets for intervention.

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Phospholipase D1 Has a Pivotal Role in Interleukin-1β-Driven Chronic Autoimmune Arthritis through Regulation of NF-κB, Hypoxia-Inducible Factor 1α, and FoxO3a

Cited by 39 publications

References 40 publications

Expression of Phospholipase D in Periodontitis and Its Role in the Inflammatory and Osteoclastic Response by Nicotine‐ and Lipopolysaccharide‐Stimulated Human Periodontal Ligament Cells

Expression of Phospholipase D in Periodontitis and Its Role in the Inflammatory and Osteoclastic Response by Nicotine‐ and Lipopolysaccharide‐Stimulated Human Periodontal Ligament Cells

Amelioration of hypoxia and LPS-induced intestinal epithelial barrier dysfunction by emodin through the suppression of the NF-κB and HIF-1α signaling pathways

Racial differences in microRNA and gene expression in hypertensive women

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