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Janus kinase 2 (JAK2) and STAT3 signaling is considered a major pathway in lipopolysaccharide (LPS)‑induced inflammation. Toll‑like receptor 4 (TLR‑4) is an inflammatory response receptor that activates JAK2 during inflammation. STAT3 is a transcription factor for the pro‑inflammatory cytokine IL‑6 in inflammation. Sulfur is an essential element in the amino acids and is required for growth and development. Non‑toxic sulfur (NTS) can be used in livestock feeds as it lacks toxicity. The present study aimed to inhibit LPS‑induced inflammation in C2C12 myoblasts using NTS by regulating TLR‑4 and JAK2/STAT3 signaling via the modulation of IL‑6. The 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay was conducted to analyze cell viability and reverse transcription polymerase chain reaction and western blotting performed to measure mRNA and protein expression levels. Chromatin immunoprecipitation and enzyme‑linked immunosorbent assays were used to determine the binding activity of proteins. The results indicated that NTS demonstrated a protective effect against LPS‑induced cell death and inhibited LPS‑induced expression of TLR‑4, JAK2, STAT3 and IL‑6. In addition, NTS inhibited the expression of nuclear phosphorylated‑STAT3 and its binding to the IL‑6 promoter. Therefore, NTS may be a potential candidate drug for the treatment of inflammation.

Titel:	Non-toxic sulfur inhibits LPS-induced inflammation by regulating TLR-4 and JAK2/STAT3 through IL-6 signaling.
Autor/in / Beteiligte Person:	Kang, DY ; Sp, N ; Jo, ES ; Rugamba, A ; Kim, HD ; Kim, IH ; Park, JC ; Bae, SW ; Jang, KJ ; Yang, YM
Zeitschrift:	Molecular medicine reports, Jg. 24 (2021-07-01), Heft 1
Veröffentlichung:	Athens, Greece : D. A. Spandidos, 2021
Medientyp:	academicJournal
ISSN:	1791-3004 (electronic)
DOI:	10.3892/mmr.2021.12124
Schlagwort:	Animals Cell Line Cytokines metabolism Gene Expression Regulation Inflammation chemically induced Inflammation genetics Janus Kinase 2 genetics Mice STAT3 Transcription Factor genetics Toll-Like Receptor 4 genetics Inflammation drug therapy Interleukin-6 metabolism Janus Kinase 2 metabolism Lipopolysaccharides adverse effects STAT3 Transcription Factor metabolism Signal Transduction drug effects Sulfur pharmacology Toll-Like Receptor 4 metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Mol Med Rep] 2021 Jul; Vol. 24 (1). <i>Date of Electronic Publication: </i>2021 Apr 28. MeSH Terms: Inflammation / drug therapy ; Interleukin-6 / metabolism ; Janus Kinase 2 / metabolism ; Lipopolysaccharides / adverse effects ; STAT3 Transcription Factor / metabolism ; Signal Transduction / drug effects ; Sulfur / pharmacology ; Toll-Like Receptor 4 / metabolism ; Animals ; Cell Line ; Cytokines / metabolism ; Gene Expression Regulation ; Inflammation / chemically induced ; Inflammation / genetics ; Janus Kinase 2 / genetics ; Mice ; STAT3 Transcription Factor / genetics ; Toll-Like Receptor 4 / genetics References: Trends Mol Med. 2007 Nov;13(11):460-9. (PMID: 18029230) ; J Cell Biochem. 2018 Jul;119(7):6094-6103. (PMID: 29574938) ; Oncotarget. 2017 Dec 14;9(6):7204-7218. (PMID: 29467962) ; J Inflamm (Lond). 2012 Jan 12;9(1):1. (PMID: 22239975) ; Endocrinology. 1999 Aug;140(8):3562-72. (PMID: 10433212) ; Curr Pharm Des. 2018;24(14):1449-1484. (PMID: 29589535) ; Curr Rheumatol Rep. 2018 Sep 19;20(11):72. (PMID: 30232562) ; Nutrients. 2018 Mar 30;10(4):. (PMID: 29601492) ; J Surg Oncol. 2003 Aug;83(4):222-6. (PMID: 12884234) ; Metabolism. 2016 Oct;65(10):1508-21. (PMID: 27621186) ; BMC Cancer. 2015 Jun 19;15:474. (PMID: 26084564) ; Methods Enzymol. 1987;143:366-76. (PMID: 3309559) ; Nutr Metab (Lond). 2007 Nov 06;4:24. (PMID: 17986345) ; Int J Oncol. 2014 Apr;44(4):1032-40. (PMID: 24430672) ; Int J Clin Exp Med. 2008;1(3):213-47. (PMID: 18997875) ; Int J Oncol. 2016 Feb;48(2):836-42. (PMID: 26648017) ; Clin Transl Sci. 2009 Feb;2(1):41-9. (PMID: 20443866) ; Biol Pharm Bull. 2009 Apr;32(4):651-6. (PMID: 19336900) ; Drugs. 2017 Apr;77(5):521-546. (PMID: 28255960) ; Immunol Rev. 2018 Nov;286(1):148-159. (PMID: 30294965) ; PLoS One. 2012;7(4):e33361. (PMID: 22485142) ; Curr Neuropharmacol. 2016;14(2):155-64. (PMID: 26639457) ; J Sports Med (Hindawi Publ Corp). 2016;2016:7498359. (PMID: 27844051) ; Drugs. 2017 Jul;77(11):1261. (PMID: 28608167) ; Science. 1994 Jun 3;264(5164):1415-21. (PMID: 8197455) ; Int J Mol Med. 2020 Mar;45(3):931-938. (PMID: 31894268) ; FASEB J. 2011 Jan;25(1):99-110. (PMID: 20826541) ; Front Immunol. 2018 Jul 26;9:1704. (PMID: 30093904) ; Semin Cell Dev Biol. 2016 Jun;54:28-41. (PMID: 26860754) ; Infect Immun. 2007 Jan;75(1):270-7. (PMID: 17074860) ; Eur Rev Med Pharmacol Sci. 2019 Feb;23(4):1770-1777. (PMID: 30840302) ; Infect Immun. 2013 Jul;81(7):2448-58. (PMID: 23630962) ; PLoS One. 2010 Aug 04;5(8):e11788. (PMID: 20694196) ; Poult Sci. 2019 Jul 1;98(7):2756-2764. (PMID: 30753670) ; Clin Exp Immunol. 2018 Jul;193(1):1-2. (PMID: 29987840) ; Am J Physiol Cell Physiol. 2003 Aug;285(2):C399-408. (PMID: 12686512) ; Signal Transduct Target Ther. 2017;2:. (PMID: 29158945) ; Biomed Pharmacother. 2016 Jul;81:318-328. (PMID: 27261609) ; Cell Mol Life Sci. 2015 Feb;72(3):557-581. (PMID: 25332099) ; Int J Mol Sci. 2018 Aug 05;19(8):. (PMID: 30081609) ; Prev Nutr Food Sci. 2016 Jun;21(2):160-4. (PMID: 27390734) Contributed Indexing: Keywords: IL-6; Janus kinase 2; STAT3; Toll-like receptor 4; non-toxic sulfur Substance Nomenclature: 0 (Cytokines) ; 0 (Interleukin-6) ; 0 (Lipopolysaccharides) ; 0 (STAT3 Transcription Factor) ; 0 (Stat3 protein, mouse) ; 0 (Tlr4 protein, mouse) ; 0 (Toll-Like Receptor 4) ; 70FD1KFU70 (Sulfur) ; EC 2.7.10.2 (Jak2 protein, mouse) ; EC 2.7.10.2 (Janus Kinase 2) Entry Date(s): Date Created: 20210428 Date Completed: 20211108 Latest Revision: 20211108 Update Code: 20231215 PubMed Central ID: PMC8127030

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