Hydrogen Sulfide Suppresses Oxidized Low-density Lipoprotein (Ox-LDL)-stimulated Monocyte Chemoattractant Protein 1 generation from Macrophages via the Nuclear Factor κB (NF-κB) Pathway

Du, Junbao; Huang, Yaqian; Yan, Hui; Zhang, Chenglong; Zhao, Manman; Zhu, Mingzhu; Liu, Jia; Chen, Stella X.; Bu, Dingfang; Tang, Chaoshu; Jin, Hongfang

doi:10.1074/jbc.m113.517995

Cited by 125 publications

(93 citation statements)

References 53 publications

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“…Our results and others [31][32][33] showed that ox-LDL also increased the IL-6 and decreased IL-10. However, IL-1β was more obviously affected by ox-LDL than IL-6 and IL-10 in our experiments.…”

Section: Discussionsupporting

confidence: 52%

C/EBPβ Acts Upstream of NF-κB P65 Subunit in Ox-LDL-Induced IL-1β Production by Macrophages

Liu

Yang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Interleukin-1β (IL-1β) is one of the critical inflammatory factors during atherogenesis. CCAAT/enhancer binding proteins β (C/EBPβ), a regulator of IL-1β production, recently been evidenced as a key player in the development of atherosclerosis. However, the mechanisms of how C/EBPβ regulates the production of IL-1β are unclear. In this study, we aimed to explore the role of C/EBPβ in regulating IL-1β production in macrophages after oxidized low-density lipoprotein (ox-LDL) exposure and the underlying mechanisms. Methods: RAW264.7 macrophages were treated with 0, 25, 50 or 100 μg/ml ox-LDL for 12, 24 or 48 h. Small interfering RNAs were used to silence related proteins. The gene and protein expression levels were determined by quantitative real-time polymerase chain reaction or western blot (WB). IL-1β secretion was assessed by enzyme-linked immunosorbent assay. The cytoplasmic and nuclear proteins were evaluated by nuclear fractionation followed by WB. Localization of p65 was observed by immunofluorescence. The binding activity of p65 to IL-1β was tested by dual-luciferase reporter assay. Results: Ox-LDL increased IL-1β production, accompanied with increasing C/EBPβ and p65 expression in a dose- and time-dependent manner. Moreover, C/EBPβ deficiency in macrophages blocked ox-LDL-induced increases in IL-1β expression, maturation as well as p65 activation. However, p65 deficiency inhibited the increase in IL-1β production, but not C/EBPβ expression. Dual-luciferase reporter results showed that overexpression of C/EBPβ significantly enhanced binding activity of p65 to IL-1β promoter. In addition, C/EBP 1β deficiency in macrophages abolished the ox-LDL-induced gene transcription increases of IL-1β, IL-6, p65 and caspase-1. Conclusions: Our results demonstrate that C/EBPβ acts upstream of NF-κB p65 subunit in ox-LDL-induced IL-1β production in macrophages and may regulate IL-1β maturation by promoting caspase-1. C/EBPβ may be a promising candidate for the prevention and treatment of atherosclerosis.

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Section: Discussionsupporting

confidence: 52%

C/EBPβ Acts Upstream of NF-κB P65 Subunit in Ox-LDL-Induced IL-1β Production by Macrophages

Liu

Yang

et al. 2018

Cell Physiol Biochem

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“…In addition, TNF-α stimulated transcription of CSE, increasing the total amount of S-sulfhydrated NF-κB. Conversely, Du et al 2014 showed recently that hydrogen sulfide suppresses oxidized low-density lipoprotein-induced macrophage inflammation by inhibiting NF-κB. This study suggests that persulfidation of C38 on p65 in fact prevents the NF-κB from leaving the cytosol, therefore completely inhibiting its DNA binding activity.…”

Section: S-sulfhydration Of Gapdh and Nf-kb Protects Against Apoptosismentioning

confidence: 62%

Persulfidation (S-sulfhydration) and H2S

Filipovic

2015

Handbook of Experimental Pharmacology

166

152

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The past decade has witnessed the discovery of hydrogen sulfide (H2S) as a new signalling molecule. Its ability to act as a neurotransmitter, regulator of blood pressure, immunomodulator or anti-apoptotic agent, together with its great pharmacological potential, is now well established. Notwithstanding the growing body of evidence showing the biological roles of H2S, the gap between the macroscopic descriptions and the actual mechanism(s) behind these processes is getting larger. The reactivity towards reactive oxygen and nitrogen species and/or metal centres cannot explain this plethora of biological effects. Therefore, a mechanism involving modification of protein cysteine residues to form protein persulfides is proposed. It is alternatively called S-sulfhydration. Persulfides are not particularly stable and show increased reactivity when compared to free thiols. Detection of protein persulfides is still facing methodological limitations, and mechanisms by which H2S causes this modification are still largely scarce. Persulfidation of protein such as KATP could contribute to H2S-induced vasodilation, while S-sulfhydration of GAPDH and NF-κB inhibits apoptosis. H2S regulates endoplasmic reticulum stress by causing persulfidation of PTP-1B. Several other proteins have been found to be regulated by this posttranslational modification of cysteine. This review article provides a critical overview of the current state of the literature addressing protein S-sulfhydration, with particular emphasis on the challenges and future research directions in this particular field.

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“…Several reports suggest that H 2 S is able to regulate activity of transcriptional factor to perform its physiological or pathophysiological effects. H 2 S inhibited nuclear factor κB activation in oxidized low‐density lipoprotein–stimulated macrophage . H 2 S stabilized hypoxia‐inducible factor 1α and increased hypoxia‐responsive gene expression in colon .…”

Section: Introductionmentioning

confidence: 96%

Hydrogen Sulfide Regulates Krüppel‐Like Factor 5 Transcription Activity via Specificity Protein 1 S‐Sulfhydration at Cys664 to Prevent Myocardial Hypertrophy

Meng

Xiao

et al. 2016

JAHA

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Hydrogen Sulfide Suppresses Oxidized Low-density Lipoprotein (Ox-LDL)-stimulated Monocyte Chemoattractant Protein 1 generation from Macrophages via the Nuclear Factor κB (NF-κB) Pathway

Cited by 125 publications

References 53 publications

C/EBPβ Acts Upstream of NF-κB P65 Subunit in Ox-LDL-Induced IL-1β Production by Macrophages

C/EBPβ Acts Upstream of NF-κB P65 Subunit in Ox-LDL-Induced IL-1β Production by Macrophages

Persulfidation (S-sulfhydration) and H2S

Hydrogen Sulfide Regulates Krüppel‐Like Factor 5 Transcription Activity via Specificity Protein 1 S‐Sulfhydration at Cys664 to Prevent Myocardial Hypertrophy

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