Sulforaphane attenuates microglia-mediated neuronal necroptosis through down-regulation of MAPK/NF-κB signaling pathways in LPS-activated BV-2 microglia

Qin, Sisi; Yang, Canhong; Huang, Weihua; Du, Shuhua; Mai, Hantao; Xiao, Jijie; Lü, Tianming

doi:10.1016/j.phrs.2018.01.014

Cited by 97 publications

(71 citation statements)

References 54 publications

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“…8,9 Inflammatory response of microglia is regulated by various pathways. 12,13 Under pathological conditions, the phosphorylation of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK) and extracellular signal regulated kinase (ERK) is markedly increased in microglia, which may lead to increased expression of pro-inflammatory phenotypes such as TNF-α, IL-1β, IL-6 and INOS. 11 Mitogen-activated protein kinases (MAPKs) are considered as the key regulators of cellular processes such as inflammatory response and cellular stress.…”

Section: Introductionmentioning

confidence: 99%

“…NF-κB is a well-defined regulatory pathway of inflammation, it was reported to promote gene expression of pro-inflammatory cytokines, many of which are up-regulated in SCI 10 ; suppression of NF-κB signalling pathway limits pro-inflammatory phenotypes and M1 polarization in microglia. 13,14 Bromodomain-containing protein 4 (BRD4) is a member of the Bromo and Extra-Terminal (BET) family; it may bind to acetylated histones and transcription factors via bromodomains and regulate diverse pathophysiological activities including inflammation. 12,13 Under pathological conditions, the phosphorylation of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK) and extracellular signal regulated kinase (ERK) is markedly increased in microglia, which may lead to increased expression of pro-inflammatory phenotypes such as TNF-α, IL-1β, IL-6 and INOS.…”

Section: Introductionmentioning

confidence: 99%

“…11 Mitogen-activated protein kinases (MAPKs) are considered as the key regulators of cellular processes such as inflammatory response and cellular stress. 12,13 Under pathological conditions, the phosphorylation of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK) and extracellular signal regulated kinase (ERK) is markedly increased in microglia, which may lead to increased expression of pro-inflammatory phenotypes such as TNF-α, IL-1β, IL-6 and INOS. 13,14 Bromodomain-containing protein 4 (BRD4) is a member of the Bromo and Extra-Terminal (BET) family; it may bind to acetylated histones and transcription factors via bromodomains and regulate diverse pathophysiological activities including inflammation.…”

Section: Introductionmentioning

confidence: 99%

“…12,13 Under pathological conditions, the phosphorylation of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK) and extracellular signal regulated kinase (ERK) is markedly increased in microglia, which may lead to increased expression of pro-inflammatory phenotypes such as TNF-α, IL-1β, IL-6 and INOS. 13,14 Bromodomain-containing protein 4 (BRD4) is a member of the Bromo and Extra-Terminal (BET) family; it may bind to acetylated histones and transcription factors via bromodomains and regulate diverse pathophysiological activities including inflammation. 15 BRD4 inhibition by JQ1 was demonstrated to attenuate LPS-induced expression of pro-inflammatory cytokines and suppressed inflammatory reactions in macrophages; 16 studies also showed that JQ1 negatively modulates inflammation in rheumatoid arthritis and osteoarthritis indicating that suppression of BRD4 might be a potential therapeutic method against inflammatory response in SCI.…”

Section: Introductionmentioning

confidence: 99%

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BRD4 inhibition attenuates inflammatory response in microglia and facilitates recovery after spinal cord injury in rats

Wang

Chen

Jin

et al. 2019

J Cellular Molecular Medi

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The pathophysiology of spinal cord injury (SCI) involves primary injury and secondary injury. For the irreversibility of primary injury, therapies of SCI mainly focus on secondary injury, whereas inflammation is considered to be a major target for secondary injury; however the regulation of inflammation in SCI is unclear and targeted therapies are still lacking. In this study, we found that the expression of BRD4 was correlated with pro‐inflammatory cytokines after SCI in rats; in vitro study in microglia showed that BRD4 inhibition either by lentivirus or JQ1 may both suppress the MAPK and NF‐κB signalling pathways, which are the two major signalling pathways involved in inflammatory response in microglia. BRD4 inhibition by JQ1 not only blocked microglial M1 polarization, but also repressed the level of pro‐inflammatory cytokines in microglia in vitro and in vivo. Furthermore, BRD4 inhibition by JQ1 can improve functional recovery and structural disorder as well as reduce neuron loss in SCI rats. Overall, this study illustrates that microglial BRD4 level is increased after SCI and BRD4 inhibition is able to suppress M1 polarization and pro‐inflammatory cytokine production in microglia which ultimately promotes functional recovery after SCI.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

BRD4 inhibition attenuates inflammatory response in microglia and facilitates recovery after spinal cord injury in rats

Wang

Chen

Jin

et al. 2019

J Cellular Molecular Medi

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“…Inhibition of class IIa histone deacetylase activity [140] Apoptosis via microtubule disruption in cancer [141] Inhibition of LPS-Induced Inflammation/cytotoxicity/oxidative microglial stress [142] Down-regulation of MAPK/NF-κB signaling in LPS-activated BV-2 microglia [143] Epigenetic modification of Nrf2 signalling in a model of AD [144] Inhibition of oxidative stress in an In-vitro model of age-related macular degeneration [145] Prevention of angiotensin II-induced cardiomyopathy by activation of Nrf2 and Akt/GSK-3ß/Fyn pathway.…”

Section: The Diverse Areas Of Application Of Sulphoraphane (Sfn) In Bmentioning

confidence: 99%

The Glucosinolates, A Sulphur Glucoside Family of Mustard Phytochemicals With Diverse Biomedical Application

Melrose¹

2019

Preprint

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This study reviewed aspects of the biology of two members of the glucosinolate family, namely sinigrin and glucoraphanin and their potential biomedical therapeutic and industrial applications. Sinigrin and glucoraphanin are converted by the -sulphoglucosidase myrosinase or the gut microbiota into their bioactive forms, allyl isothiocyanate (AITC) and sulphoraphanin (SFN) which constitute part of a sophisticated defence mechanism plants have developed over several hundred million years of evolution to protect them from parasitic attack from aphids, ticks and nematodes.These compounds display biological activities in a number of mammalian physiological processes and potential biotherapeutic application. Glucosinolates may be useful in bio-fumigation and treatment of biofilms which occur on plant equipment and medical implants formed by problematic pathogenic bacteria such as Pseudomonas aeruginosa. AITC and SFN display similar antibiotic activity as Vancomycin in the treatment of bacteria listed by the World Health Organization as antibiotic-resistant "priority pathogens".AITC and SFN also display bioactivity in cancer chemoprevention through the induction of phase II antioxidant enzymes which inactivate potential carcinogens. The glucosinolates have found application in the prevention of bacterial and fungal spoilage of food substances during processing and in advanced food packaging formats which improve the shelf-life of food products.

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Sulforaphane suppresses lipopolysaccharide‐ and Pam3CysSerLys4‐mediated inflammation in chronic obstructive pulmonary disease via toll‐like receptors

2021

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Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disease of the airway that represents a large global disease burden. Inflammation is a prominent feature of COPD and represents an important target for treatment. Toll‐like receptors (TLRs) are pattern recognition receptors that detect invading microorganisms and nonmicrobial endogenous molecules to trigger inflammatory responses during host defense and tissue repair. The TLR signaling pathway is closely linked to the pathogenesis of COPD. Sulforaphane (SFN), an isothiocyanate derived from cruciferous vegetables, is well known for its anti‐inflammatory activities. However, the molecular function of SFN in inhibition of COPD inflammation has yet to be fully elucidated. In this study, we investigated the effects of SFN on lipopolysaccharide (LPS)‐ or Pam3CysSerLys4 (Pam3CSK4)‐induced inflammation in monocyte‐derived macrophages (MDMs) from patients with COPD. MDMs from patients with COPD showed higher expression levels of TLR2, TLR4 and downstream myeloid differentiation factor 88 (MyD88) than healthy controls, along with increased secretion of interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNF‐α) ( P < 0.05). Stimulation with TLR ligands (Pam3CSK4 and LPS) up‐regulated the levels of TLR2, TLR4 and MyD88 in MDMs from patients with COPD and induced the release of IL‐6 and TNF‐α ( P < 0.05). Pretreatment of MDMs from patients with COPD with SFN significantly suppressed Pam3CSK4‐ or LPS‐induced TLR2, TLR4 and MyD88 expression, along with a reduction in the production of IL‐6 and TNF‐α ( P < 0.05). Collectively, these data indicate that SFN exerts its anti‐inflammatory activity in COPD by modulating the TLR pathway. SFN may represent a potential therapeutic agent for the treatment of COPD.

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Sulforaphane attenuates microglia-mediated neuronal necroptosis through down-regulation of MAPK/NF-κB signaling pathways in LPS-activated BV-2 microglia

Cited by 97 publications

References 54 publications

BRD4 inhibition attenuates inflammatory response in microglia and facilitates recovery after spinal cord injury in rats

BRD4 inhibition attenuates inflammatory response in microglia and facilitates recovery after spinal cord injury in rats

The Glucosinolates, A Sulphur Glucoside Family of Mustard Phytochemicals With Diverse Biomedical Application

Sulforaphane suppresses lipopolysaccharide‐ and Pam3CysSerLys4‐mediated inflammation in chronic obstructive pulmonary disease via toll‐like receptors

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