Non-toxic sulfur inhibits LPS-induced inflammation by regulating TLR-4 and JAK2/STAT3 through IL-6 signaling

Kang, Dong Young; Sp, Nipin; Jo, Eun Seong; Rugamba, Alexis; Kim, Hyoung Do; Kim, Il Ho; Park, Jongchan; Bae, Se Won; Jang, Kyoung‐Jin; Yang, Young Mok

doi:10.3892/mmr.2021.12124

Cited by 17 publications

(11 citation statements)

References 43 publications

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“…In addition, it has been previously shown that activation of JAK2 and STAT3 also affects IL‐6 63 . However, it is known that the formation of cellular damage is reduced as a result of inhibition of the IL‐6/JAK2/STAT3 pathway 64–66 . In the present study, it was determined that CYP administration triggered IL‐6 expression and increased JAK2 and STAT3 mRNA transcription, possibly related to IL‐6 up‐regulation.…”

Section: Discussionmentioning

confidence: 47%

“…63 However, it is known that the formation of cellular damage is reduced as a result of inhibition of the IL-6/JAK2/STAT3 pathway. [64][65][66] In the present study, it was determined that CYP administration triggered IL-6 expression and increased JAK2 and STAT3 mRNA transcription, possibly related to IL-6 up-regulation. However, it was observed that QUE suppressed the IL-6 gene and thus interrupted the JAK2/STAT3 pathway.…”

Section: Discussionmentioning

confidence: 75%

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Evaluation of protective effects of quercetin against cypermethrin‐induced lung toxicity in rats via oxidative stress, inflammation, apoptosis, autophagy, and endoplasmic reticulum stress pathway

İleritürk

Kandemir

2022

Environmental Toxicology

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Cypermethrin (CYP), a type II synthetic pyrethroid, is the most widely used insecticide worldwide. Inhalation of it may cause side effects. This study is aimed to examine potential protection of quercetin (QUE) which is a well-known antioxidant in CYPinduced lung toxicity. Accordingly, 35 Spraque Dawley male rats were divided into five equal groups as follows: I-Control group, II-QUE group (50 mg/kg/b.w. QUE), III-CYP group (25 mg/kg/b.w. CYP), IV-CYP + QUE 25 (25 mg/kg/b.w. CYP + 25 mg/ kg/b.w. QUE), V-CYP + QUE (25 mg/kg/b.w. CYP + 50 mg/kg/b.w. QUE) were treated with oral gavage throughout 28 days. CYP intoxication was associated with increased malondialdehyde level while glutathione concentration, activities of glutathione peroxidase, superoxide dismutase, and catalase reduced. CYP adminisitration caused of apoptosis in the lung by up-regulating caspase-3 and Bax levels and down-regulating Bcl-2. CYP also caused of endoplasmic reticulum (ER) stress by increasing mRNA transcript levels of PERK, IRE1, ATF6, and GRP78. Additionally, it was observed that CYP administration activated IL-6/JAK2/STAT3/MAPK14 signaling pathway and levels of IL-1β, NF-κB, TNF-α, and iNOS in the lung tissue. Therefore, it was determined that CYP administration triggered autophagy by upregulating LC3A and LC3B mRNA transcript levels. Moreover, the protein levels of NF-κB, caspase-3, Bax, Bcl-2, and cytochorme-c were examined by Western blot analysis. However, cotreatment with QUE at a dose of 25 and 50 mg/kg considerably protective oxidative stress, inflammation, apoptosis, ER stress, autophagy, and IL-6/JAK2/STAT3/MAPK14 signaling pathway in lung tissue. Overall, the findings of this study suggest that lung damage associated with CYP toxicity could be protected by QUE administration.

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Section: Discussionmentioning

confidence: 47%

Section: Discussionmentioning

confidence: 75%

Evaluation of protective effects of quercetin against cypermethrin‐induced lung toxicity in rats via oxidative stress, inflammation, apoptosis, autophagy, and endoplasmic reticulum stress pathway

İleritürk

Kandemir

2022

Environmental Toxicology

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“…TLRs play a role in the immune system by directly recognizing different pathogen-related molecular patterns (PAMP) [ 33 ] in nonspecific immunity after the stressor penetrates the physical barrier of the human body. As a member of the TLR family, TLR4 is expressed mainly on the membranes of macrophages and plays an important role in the inflammatory response [ 34 ]. Besides recognizing inflammatory stressors, TLR4 also recognizes ox-LDL and further aggravates lipid stasis in macrophages.…”

Section: Discussionmentioning

confidence: 99%

Histone Deacetylase9 Represents the Epigenetic Promotion of M1 Macrophage Polarization and Inflammatory Response via TLR4 Regulation

Cao

Zhang

et al. 2022

BioMed Research International

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Atherosclerosis is a chronic inflammatory response mediated by various factors, where epigenetic regulation involving histone deacetylation is envisaged to modulate the expression of related proteins by regulating the binding of transcription factors to DNA, thereby influencing the development of atherosclerosis. The mechanism of atherosclerosis by histone deacetylation is partly known; hence, this project aimed at investigating the role of histone deacetylase 9 (HDAC9) in atherosclerosis. For this purpose, serum was separated from blood samples following clotting and centrifugation from atherosclerotic and healthy patients ( n = 40 each), and then, various tests were performed. The results indicated that toll-like receptor 4 (TLR4) was not only positively correlated to the HDAC9 gene, but was also upregulated in atherosclerosis, where it was also significantly upregulated in the atherosclerosis cell model of oxidized low-density lipoprotein-induced macrophages. Conversely, the TLR4 was significantly downregulated in instances of loss of HDAC9 function, cementing the bridging relationship between HDAC9 and macrophage polarization, where the HDAC9 was found to upregulate M1 macrophage polarization which translated into the release of higher content of proinflammatory cytokines such as interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), which tend to significantly decrease following the deletion of TLR4. Hence, this study reports novel relation between epigenetic control and atherosclerosis, which could partly be explained by histone deacetylation.

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“…The IL-6/JAK/ STAT3 pathway is a major signaling pathway involved in regulating the inflammatory response in disease pathogenesis. JAK/STAT3 signaling promotes inflammation by regulating the development of innate lymphocytes in the immune response (Kang et al, 2021). STAT3 plays a central role in JAK/STAT signaling (You et al, 2015).…”

Section: Glycyrol May Affect Cell Proliferation and Survival By Regul...mentioning

confidence: 99%

Exploring the mechanism of action of licorice in the treatment of COVID-19 through bioinformatics analysis and molecular dynamics simulation

Cao

Gong²,

Wu³

et al. 2022

Front. Pharmacol.

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Purpose: The rapid worldwide spread of Corona Virus Disease 2019 (COVID-19) has become not only a global challenge, but also a lack of effective clinical treatments. Studies have shown that licorice can significantly improve clinical symptoms such as fever, dry cough and shortness of breath in COVID-19 patients with no significant adverse effects. However, there is still a lack of in-depth analysis of the specific active ingredients of licorice in the treatment of COVID-19 and its mechanism of action. Therefore, we used molecular docking and molecular dynamics to explore the mechanism of action of licorice in the treatment of COVID-19.Methods: We used bioinformatics to screen active pharmaceutical ingredients and potential targets, the disease-core gene target-drug network was established and molecular docking was used for verification. Molecular dynamics simulations were carried out to verify that active ingredients were stably combined with protein targets. The supercomputer platform was used to measure and analyze stability of protein targets at the residue level, solvent accessible surface area, number of hydrogen bonds, radius of gyration and binding free energy.Results: Licorice had 255 gene targets, COVID-19 had 4,628 gene targets, the intersection gene targets were 101. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene ontology (GO) analysis showed that licorice played an important role mainly through the signaling pathways of inflammatory factors and oxidative stress. Molecular docking showed that Glycyrol, Phaseol and Glyasperin F in licorice may playe a role in treating COVID-19 by acting on STAT3, IL2RA, MMP1, and CXCL8. Molecular dynamics were used to demonstrate and analyze the binding stability of active ingredients to protein targets.Conclusion: This study found that Phaseol in licorice may reduce inflammatory cell activation and inflammatory response by inhibiting the activation of CXCL8 and IL2RA; Glycyrol may regulate cell proliferation and survival by acting on STAT3. Glyasperin F may regulate cell growth by inhibiting the activation of MMP1, thus reducing tissue damage and cell death caused by excessive inflammatory response and promoting the growth of new tissues. Therefore, licorice is proposed as an effective candidate for the treatment of COVID-19 through STAT3, IL2RA, MMP1, and CXCL8.

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Non-toxic sulfur inhibits LPS-induced inflammation by regulating TLR-4 and JAK2/STAT3 through IL-6 signaling

Cited by 17 publications

References 43 publications

Evaluation of protective effects of quercetin against cypermethrin‐induced lung toxicity in rats via oxidative stress, inflammation, apoptosis, autophagy, and endoplasmic reticulum stress pathway

Evaluation of protective effects of quercetin against cypermethrin‐induced lung toxicity in rats via oxidative stress, inflammation, apoptosis, autophagy, and endoplasmic reticulum stress pathway

Histone Deacetylase9 Represents the Epigenetic Promotion of M1 Macrophage Polarization and Inflammatory Response via TLR4 Regulation

Exploring the mechanism of action of licorice in the treatment of COVID-19 through bioinformatics analysis and molecular dynamics simulation

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