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Background and Objective: Pulmonary fibrosis caused by lung injury is accompanied by varying degrees of inflammation, and diazepam can reduce the levels of inflammatory factors. Therefore, the purpose of this study was to determine whether diazepam can inhibit inflammation and ameliorate pulmonary fibrosis by regulating the let-7a-5p/myeloid differentiation factor 88 (MYD88) axis.

Methods: Lipopolysaccharide (LPS) was used to induce cell pyroptosis in an animal model of pulmonary fibrosis. After treatment with diazepam, changes in cell proliferation and apoptosis were observed, and the occurrence of inflammation and pulmonary fibrosis in the mice was detected.

Results: The results showed that LPS can successfully induce cell pyroptosis and inflammatory responses and cause lung fibrosis in mice. Diazepam inhibits the expression of pyroptosis-related factors and inflammatory factors; moreover, it attenuates the occurrence of pulmonary fibrosis in mice. Mechanistically, diazepam can upregulate the expression of let-7a-5p, inhibit the expression of MYD88, and reduce inflammation and inhibit pulmonary fibrosis by regulating the let-7a-5p/MYD88 axis.

Conclusion: Our findings indicated that diazepam can inhibit LPS-induced pyroptosis and inflammatory responses and alleviate pulmonary fibrosis in mice by regulating the let-7a-5p/MYD88 axis.

Competing Interests: The authors have declared that no competing interests exist.

(Copyright: © 2024 Song et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Titel:	Diazepam inhibits LPS-induced pyroptosis and inflammation and alleviates pulmonary fibrosis in mice by regulating the let-7a-5p/MYD88 axis.
Autor/in / Beteiligte Person:	Song, D ; Tang, X ; Du, J ; Tao, K ; Li, Y
Link:	Full Text Finder (Volltext)
Zeitschrift:	PloS one, Jg. 19 (2024-06-14), Heft 6, S. e0305409
Veröffentlichung:	San Francisco, CA : Public Library of Science, 2024
Medientyp:	academicJournal
ISSN:	1932-6203 (electronic)
DOI:	10.1371/journal.pone.0305409
Schlagwort:	Animals Mice Male Mice, Inbred C57BL Disease Models, Animal Signal Transduction drug effects Pyroptosis drug effects Lipopolysaccharides Diazepam pharmacology Pulmonary Fibrosis drug therapy Pulmonary Fibrosis pathology Pulmonary Fibrosis metabolism Myeloid Differentiation Factor 88 metabolism Myeloid Differentiation Factor 88 genetics MicroRNAs genetics MicroRNAs metabolism Inflammation drug therapy Inflammation pathology Inflammation metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [PLoS One] 2024 Jun 14; Vol. 19 (6), pp. e0305409. <i>Date of Electronic Publication: </i>2024 Jun 14 (<i>Print Publication: </i>2024). MeSH Terms: Pyroptosis* / drug effects ; Lipopolysaccharides* ; Diazepam* / pharmacology ; Pulmonary Fibrosis* / drug therapy ; Pulmonary Fibrosis* / pathology ; Pulmonary Fibrosis* / metabolism ; Myeloid Differentiation Factor 88* / metabolism ; Myeloid Differentiation Factor 88* / genetics ; MicroRNAs* / genetics ; MicroRNAs* / metabolism ; Inflammation* / drug therapy ; Inflammation* / pathology ; Inflammation* / metabolism ; Animals ; Mice ; Male ; Mice, Inbred C57BL ; Disease Models, Animal ; Signal Transduction / drug effects References: N Engl J Med. 2015 Mar 26;372(13):1189-91. (PMID: 25806913) ; Eur Respir J. 2016 Mar;47(3):910-8. (PMID: 26743485) ; Inhal Toxicol. 2018 Mar - Apr;30(4-5):187-194. (PMID: 30257148) ; Elife. 2018 Dec 07;7:. (PMID: 30526845) ; Int Immunopharmacol. 2010 Nov;10(11):1335-43. (PMID: 20846531) ; Respir Res. 2016 Apr 12;17:39. (PMID: 27071460) ; Curr Biol. 2016 Jul 11;26(13):R568-R572. (PMID: 27404251) ; Biomed Pharmacother. 2020 Jan;121:109595. (PMID: 31710896) ; Exp Cell Res. 2018 Jan 15;362(2):489-497. (PMID: 29258746) ; Cytokine. 2015 Nov;76(1):25-37. (PMID: 26185894) ; Vet Immunol Immunopathol. 2003 Sep 15;95(1-2):11-9. (PMID: 12969632) ; J Biol Regul Homeost Agents. 2019 Sep 26;33(5):1415-1424. (PMID: 31556264) ; Semin Respir Crit Care Med. 2020 Apr;41(2):177-183. (PMID: 32279289) ; Front Immunol. 2013 Nov 20;4:396. (PMID: 24312101) ; J Neuroimmunol. 2015 May 15;282:97-103. (PMID: 25903735) ; Am J Respir Crit Care Med. 2010 Sep 1;182(5):643-51. (PMID: 20522792) ; J Biol Chem. 2017 Jul 7;292(27):11336-11347. (PMID: 28536261) ; Respir Res. 2017 Oct 16;18(1):177. (PMID: 29037205) ; J Pathol. 2015 Jul;236(3):384-94. (PMID: 25779936) ; Part Fibre Toxicol. 2014 Nov 19;11:58. (PMID: 25406505) ; Neuroimmunomodulation. 2015;22(5):293-302. (PMID: 25721617) ; Front Genet. 2017 Mar 28;8:31. (PMID: 28400788) ; Annu Rev Med. 2004;55:395-417. (PMID: 14746528) ; BMC Cancer. 2018 Feb 7;18(1):159. (PMID: 29415668) ; Cell Cycle. 2008 Mar 15;7(6):759-64. (PMID: 18344688) ; Cell Tissue Res. 2017 Mar;367(3):607-626. (PMID: 27981380) ; J Cell Mol Med. 2016 Nov;20(11):2064-2077. (PMID: 27306439) ; J Neuroimmunol. 2017 Dec 15;313:145-151. (PMID: 28992974) ; Expert Opin Ther Targets. 2018 May;22(5):401-408. (PMID: 29658361) ; N Engl J Med. 2001 Aug 16;345(7):517-25. (PMID: 11519507) ; Mol Med. 2022 Jun 25;28(1):72. (PMID: 35752760) ; N Engl J Med. 2014 May 29;370(22):2071-82. (PMID: 24836310) ; Immunity. 2015 Nov 17;43(5):835-7. (PMID: 26588774) ; Int Immunopharmacol. 2019 Jul;72:112-123. (PMID: 30974282) ; Am J Respir Cell Mol Biol. 2009 Dec;41(6):661-70. (PMID: 19265174) ; Toxicology. 2011 Jul 11;285(1-2):25-30. (PMID: 21473897) ; Eur Respir J. 2014 Jan;43(1):276-85. (PMID: 23520315) ; Cell Biol Int. 2018 Sep;42(10):1311-1320. (PMID: 29907991) ; Am J Physiol Lung Cell Mol Physiol. 2019 Mar 1;316(3):L567-L577. (PMID: 30652497) ; Cell. 2008 Jan 11;132(1):9-14. (PMID: 18191211) ; Nature. 2015 Oct 29;526(7575):660-5. (PMID: 26375003) ; Neuroscience. 2011 Dec 29;199:421-8. (PMID: 21964471) ; Gene. 2018 Dec 30;679:232-240. (PMID: 30201337) ; Biomed Pharmacother. 2019 Oct;118:109239. (PMID: 31351431) ; Cell Mol Gastroenterol Hepatol. 2016 Mar 19;2(4):439-453. (PMID: 27777967) ; Respir Investig. 2019 Jul;57(4):300-311. (PMID: 30853366) ; Innate Immun. 2012 Dec;18(6):846-55. (PMID: 22522429) Substance Nomenclature: 0 (Lipopolysaccharides) ; Q3JTX2Q7TU (Diazepam) ; 0 (Myeloid Differentiation Factor 88) ; 0 (MicroRNAs) ; 0 (mirnlet7 microRNA, mouse) ; 0 (Myd88 protein, mouse) Entry Date(s): Date Created: 20240614 Date Completed: 20240614 Latest Revision: 20240618 Update Code: 20240618 PubMed Central ID: PMC11178199

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Diazepam inhibits LPS-induced pyroptosis and inflammation and alleviates pulmonary fibrosis in mice by regulating the let-7a-5p/MYD88 axis.