Cyclic adenosine monophosphate critically modulates cardiac GLP-1 receptor's anti-inflammatory effects.
Cardiac myocyte
Cyclic adenosine monophosphate
Cytokines
GLP-1 receptor
Inflammation
Liraglutide
Matrix metalloproteinase
Phosphodiesterase-4 inhibitor
Signal transduction
Journal
Inflammation research : official journal of the European Histamine Research Society ... [et al.]
ISSN: 1420-908X
Titre abrégé: Inflamm Res
Pays: Switzerland
ID NLM: 9508160
Informations de publication
Date de publication:
21 Sep 2024
21 Sep 2024
Historique:
received:
03
06
2024
accepted:
12
09
2024
revised:
09
09
2024
medline:
21
9
2024
pubmed:
21
9
2024
entrez:
21
9
2024
Statut:
aheadofprint
Résumé
Glucagon-like peptide (GLP)-1 receptor (GLP1R) agonists exert a multitude of beneficial cardiovascular effects beyond control of blood glucose levels and obesity reduction. They also have anti-inflammatory actions through both central and peripheral mechanisms. GLP1R is a G protein-coupled receptor (GPCR), coupling to adenylyl cyclase (AC)-stimulatory Gs proteins to raise cyclic 3`-5`-adenosine monophosphate (cAMP) levels in cells. cAMP exerts various anti-apoptotic and anti-inflammatory effects via its effectors protein kinase A (PKA) and Exchange protein directly activated by cAMP (Epac). However, the precise role and importance of cAMP in mediating GLP1R`s anti-inflammatory actions, at least in the heart, remains to be determined. To this end, we tested the effects of the GLP1R agonist liraglutide on lipopolysaccharide (LPS)-induced acute inflammatory injury in H9c2 cardiac cells, either in the absence of cAMP production (AC inhibition) or upon enhancement of cAMP levels via phosphodiesterase (PDE)-4 inhibition with roflumilast. Liraglutide dose-dependently inhibited LPS-induced apoptosis and increased cAMP levels in H9c2 cells, with roflumilast but also PDE8 inhibition further enhancing cAMP production by liraglutide. GLP1R-stimulated cAMP markedly suppressed the LPS-dependent induction of pro-inflammatory tumor necrosis factor (TNF)-a, interleukin (IL)-1b, and IL-6 cytokine expression, of inducible nitric oxide synthase (iNOS) expression and nuclear factor (NF)-kB activity, of matrix metalloproteinases (MMP)-2 and MMP-9 levels and activities, and of myocardial injury markers in H9c2 cardiac cells. The effects of liraglutide were mediated by the GLP1R since they were abolished by the GLP1R antagonist exendin(9-39). Importantly, AC inhibition completely abrogated liraglutide`s suppression of LPS-dependent inflammatory injury, whereas roflumilast significantly enhanced the protective effects of liraglutide against LPS-induced inflammation. Finally, PKA inhibition or Epac1/2 inhibition alone only partially blocked liraglutide`s suppression of LPS-induced inflammation in H9c2 cardiac cells, but, together, PKA and Epac1/2 inhibition fully prevented liraglutide from reducing LPS-dependent inflammation. cAMP, via activation of both PKA and Epac, is essential for GLP1R`s anti-inflammatory signaling in cardiac cells and that cAMP levels crucially regulate the anti-inflammatory efficacy of GLP1R agonists in the heart. Strategies that elevate cardiac cAMP levels, such as PDE4 inhibition, may potentiate the cardiovascular, including anti-inflammatory, benefits of GLP1R agonist drugs.
Sections du résumé
BACKGROUND
BACKGROUND
Glucagon-like peptide (GLP)-1 receptor (GLP1R) agonists exert a multitude of beneficial cardiovascular effects beyond control of blood glucose levels and obesity reduction. They also have anti-inflammatory actions through both central and peripheral mechanisms. GLP1R is a G protein-coupled receptor (GPCR), coupling to adenylyl cyclase (AC)-stimulatory Gs proteins to raise cyclic 3`-5`-adenosine monophosphate (cAMP) levels in cells. cAMP exerts various anti-apoptotic and anti-inflammatory effects via its effectors protein kinase A (PKA) and Exchange protein directly activated by cAMP (Epac). However, the precise role and importance of cAMP in mediating GLP1R`s anti-inflammatory actions, at least in the heart, remains to be determined. To this end, we tested the effects of the GLP1R agonist liraglutide on lipopolysaccharide (LPS)-induced acute inflammatory injury in H9c2 cardiac cells, either in the absence of cAMP production (AC inhibition) or upon enhancement of cAMP levels via phosphodiesterase (PDE)-4 inhibition with roflumilast.
METHODS & RESULTS
RESULTS
Liraglutide dose-dependently inhibited LPS-induced apoptosis and increased cAMP levels in H9c2 cells, with roflumilast but also PDE8 inhibition further enhancing cAMP production by liraglutide. GLP1R-stimulated cAMP markedly suppressed the LPS-dependent induction of pro-inflammatory tumor necrosis factor (TNF)-a, interleukin (IL)-1b, and IL-6 cytokine expression, of inducible nitric oxide synthase (iNOS) expression and nuclear factor (NF)-kB activity, of matrix metalloproteinases (MMP)-2 and MMP-9 levels and activities, and of myocardial injury markers in H9c2 cardiac cells. The effects of liraglutide were mediated by the GLP1R since they were abolished by the GLP1R antagonist exendin(9-39). Importantly, AC inhibition completely abrogated liraglutide`s suppression of LPS-dependent inflammatory injury, whereas roflumilast significantly enhanced the protective effects of liraglutide against LPS-induced inflammation. Finally, PKA inhibition or Epac1/2 inhibition alone only partially blocked liraglutide`s suppression of LPS-induced inflammation in H9c2 cardiac cells, but, together, PKA and Epac1/2 inhibition fully prevented liraglutide from reducing LPS-dependent inflammation.
CONCLUSIONS
CONCLUSIONS
cAMP, via activation of both PKA and Epac, is essential for GLP1R`s anti-inflammatory signaling in cardiac cells and that cAMP levels crucially regulate the anti-inflammatory efficacy of GLP1R agonists in the heart. Strategies that elevate cardiac cAMP levels, such as PDE4 inhibition, may potentiate the cardiovascular, including anti-inflammatory, benefits of GLP1R agonist drugs.
Identifiants
pubmed: 39305297
doi: 10.1007/s00011-024-01950-0
pii: 10.1007/s00011-024-01950-0
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NHLBI NIH HHS
ID : HL155718-01
Pays : United States
Organisme : American Foundation for Pharmaceutical Education
ID : 333325-2017
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Références
Diz-Chaves Y, Mastoor Z, Spuch C, González-Matías LC, Mallo F. Anti-inflammatory effects of GLP-1 receptor activation in the brain in neurodegenerative diseases. Int J Mol Sci. 2022;23(17):9583.
pubmed: 36076972
pmcid: 9455625
doi: 10.3390/ijms23179583
Klen J, Dolžan V. Glucagon-like peptide-1 receptor agonists in the management of type 2 diabetes mellitus and obesity: the impact of pharmacological properties and genetic factors. Int J Mol Sci. 2022;23(7):3451.
pubmed: 35408810
pmcid: 8998939
doi: 10.3390/ijms23073451
Ussher JR, Drucker DJ. Glucagon-like peptide 1 receptor agonists: cardiovascular benefits and mechanisms of action. Nat Rev Cardiol. 2023;20(7):463–74.
pubmed: 36977782
doi: 10.1038/s41569-023-00849-3
Pandey S, Mangmool S, Parichatikanond W. Multifaceted roles of GLP-1 and its analogs: a review on molecular mechanisms with a cardiotherapeutic perspective. Pharmaceuticals (Basel). 2023;16(6):836.
pubmed: 37375783
doi: 10.3390/ph16060836
Bendotti G, Montefusco L, Lunati ME, Usuelli V, Pastore I, Lazzaroni E, Assi E, Seelam AJ, El Essawy B, Jang J, Loretelli C, D’Addio F, Berra C, Ben Nasr M, Zuccotti G, Fiorina P. The anti-inflammatory and immunological properties of GLP-1 receptor agonists. Pharmacol Res. 2022;182: 106320.
pubmed: 35738455
doi: 10.1016/j.phrs.2022.106320
Lee YS, Jun HS. Anti-inflammatory effects of GLP-1-based therapies beyond glucose control. Mediators Inflamm. 2016;2016:3094642.
pubmed: 27110066
pmcid: 4823510
doi: 10.1155/2016/3094642
Graaf Cd, Donnelly D, Wootten D, Lau J, Sexton PM, Miller LJ, Ahn JM, Liao J, Fletcher MM, Yang D, Brown AJ, Zhou C, Deng J, Wang MW. Glucagon-like peptide-1 and its class B G protein-coupled receptors: a long march to therapeutic successes. Pharmacol Rev. 2016;68(4):954–1013.
pubmed: 27630114
pmcid: 5050443
doi: 10.1124/pr.115.011395
Wang R, Wang N, Han Y, Xu J, Xu Z. Dulaglutide alleviates LPS-induced injury in cardiomyocytes. ACS Omega. 2021;6(12):8271–8.
pubmed: 33817486
pmcid: 8015136
doi: 10.1021/acsomega.0c06326
Nuamnaichati N, Mangmool S, Chattipakorn N, Parichatikanond W. Stimulation of GLP-1 receptor inhibits methylglyoxal-induced mitochondrial dysfunctions in H9c2 cardiomyoblasts: potential role of Epac/PI3K/Akt pathway. Front Pharmacol. 2020;29(11):805.
doi: 10.3389/fphar.2020.00805
Lu K, Chang G, Ye L, Zhang P, Li Y, Zhang D. Protective effects of extendin-4 on hypoxia/reoxygenation-induced injury in H9c2 cells. Mol Med Rep. 2015;12(2):3007–16.
pubmed: 25936390
doi: 10.3892/mmr.2015.3682
Zhu Q, Luo Y, Wen Y, Wang D, Li J, Fan Z. Semaglutide inhibits ischemia/reperfusion-induced cardiomyocyte apoptosis through activating PKG/PKCε/ERK1/2 pathway. Biochem Biophys Res Commun. 2023;5(647):1–8.
Cui X, Liang H, Hao C, Jing X. Liraglutide preconditioning attenuates myocardial ischemia/ reperfusion injury via homer1 activation. Aging (Albany NY). 2021;13(5):6625–33.
pubmed: 33535171
doi: 10.18632/aging.202429
Wu XM, Ou QY, Zhao W, Liu J, Zhang H. The GLP-1 analogue liraglutide protects cardiomyocytes from high glucose-induced apoptosis by activating the Epac-1/Akt pathway. Exp Clin Endocrinol Diabetes. 2014;122(10):608–14.
pubmed: 25140997
doi: 10.1055/s-0034-1384584
Ding W, Chang WG, Guo XC, Liu Y, Xiao DD, Ding D, Wang JX, Zhang XJ. Exenatide protects against cardiac dysfunction by attenuating oxidative stress in the diabetic mouse heart. Front Endocrinol (Lausanne). 2019;5(10):202.
doi: 10.3389/fendo.2019.00202
Chang G, Liu J, Qin S, Jiang Y, Zhang P, Yu H, Lu K, Zhang N, Cao L, Wang Y, Li Y, Zhang D. Cardioprotection by exenatide: a novel mechanism via improving mitochondrial function involving the GLP-1 receptor/cAMP/PKA pathway. Int J Mol Med. 2018;41(3):1693–703.
pubmed: 29286061
Papasergi-Scott MM, Pérez-Hernández G, Batebi H, Gao Y, Eskici G, Seven AB, Panova O, Hilger D, Casiraghi M, He F, Maul L, Gmeiner P, Kobilka BK, Hildebrand PW, Skiniotis G. Time-resolved cryo-EM of G-protein activation by a GPCR. Nature. 2024;629(8014):1182–91.
pubmed: 38480881
doi: 10.1038/s41586-024-07153-1
Willard FS, Sloop KW. Physiology and emerging biochemistry of the glucagon-like peptide-1 receptor. Exp Diabetes Res. 2012;2012: 470851.
pubmed: 22666230
pmcid: 3359799
doi: 10.1155/2012/470851
Tavares LP, Negreiros-Lima GL, Lima KM, Silva PMR, Pinho V, Teixeira MM, Sousa LP. Blame the signaling: role of cAMP for the resolution of inflammation. Pharmacol Res. 2020;159:105030.
pubmed: 32562817
doi: 10.1016/j.phrs.2020.105030
Crowley EL, Gooderham MJ. Phosphodiesterase-4 inhibition in the management of psoriasis. Pharmaceutics. 2023;16(1):23.
pubmed: 38258034
pmcid: 10819567
doi: 10.3390/pharmaceutics16010023
Violi F, Castellani V, Menichelli D, Pignatelli P, Pastori D. Gut barrier dysfunction and endotoxemia in heart failure: a dangerous connubium? Am Heart J. 2023;264:40–8.
pubmed: 37301317
doi: 10.1016/j.ahj.2023.06.002
Dessauer CW, Watts VJ, Ostrom RS, Conti M, Dove S, Seifert R. International union of basic and clinical pharmacology. CI. Structures and small molecule modulators of mammalian adenylyl cyclases. Pharmacol Rev. 2017;69(2):93–139.
pubmed: 28255005
pmcid: 5394921
doi: 10.1124/pr.116.013078
Danowitz M, De Leon DD. The role of GLP-1 signaling in hypoglycemia due to hyperinsulinism. Front Endocrinol (Lausanne). 2022;24(13): 863184.
doi: 10.3389/fendo.2022.863184
Kim GE, Kass DA. Cardiac phosphodiesterases and their modulation for treating heart disease. Handb Exp Pharmacol. 2017;243:249–69.
pubmed: 27787716
pmcid: 5665023
doi: 10.1007/164_2016_82
Tsai LC, Beavo JA. The roles of cyclic nucleotide phosphodiesterases (PDEs) in steroidogenesis. Curr Opin Pharmacol. 2011;11(6):670–5.
pubmed: 21962440
pmcid: 4034742
doi: 10.1016/j.coph.2011.09.003
Soderling SH, Beavo JA. Regulation of cAMP and cGMP signaling: new phosphodiesterases and new functions. Curr Opin Cell Biol. 2000;12(2):174–9.
pubmed: 10712916
doi: 10.1016/S0955-0674(99)00073-3
Turner MJ, Sato Y, Thomas DY, Abbott-Banner K, Hanrahan JW. Phosphodiesterase 8A regulates CFTR activity in airway epithelial cells. Cell Physiol Biochem. 2021;55(6):784–804.
pubmed: 34936285
doi: 10.33594/000000477
Han CK, Tien YC, Jine-Yuan Hsieh D, Ho TJ, Lai CH, Yeh YL, Hsuan Day C, Shen CY, Hsu HH, Lin JY, Huang CY. Attenuation of the LPS-induced, ERK-mediated upregulation of fibrosis-related factors FGF-2, uPA, MMP-2, and MMP-9 by Carthamus tinctorius L in cardiomyoblasts. Environ Toxicol. 2017;32(3):754–63.
pubmed: 27098997
doi: 10.1002/tox.22275
Cai X, Cai J, Fang L, Xu S, Zhu H, Wu S, Chen Y, Fang S. Design, synthesis and molecular modeling of novel D-ring substituted steroidal 4,5-dihydropyrazole thiazolinone derivatives as anti-inflammatory agents by inhibition of COX-2/iNOS production and down-regulation of NF-κB/MAPKs in LPS-induced RAW264.7 macrophage cells. Eur J Med Chem. 2024;272:116460.
pubmed: 38704943
doi: 10.1016/j.ejmech.2024.116460
Lee JK, Wang X, Wang J, Rosales JL, Lee KY. PKA inhibition kills L-asparaginase-resistant leukemic cells from relapsed acute lymphoblastic leukemia patients. Cell Death Discov. 2024;10(1):257.
pubmed: 38802344
pmcid: 11130271
doi: 10.1038/s41420-024-02028-w
Tomilin VN, Pyrshev K, Stavniichuk A, Hassanzadeh Khayyat N, Ren G, Zaika O, Khedr S, Staruschenko A, Mei FC, Cheng X, Pochynyuk O. Epac1-/- and Epac2-/- mice exhibit deficient epithelial Na+ channel regulation and impaired urinary Na+ conservation. JCI Insight. 2022;7(3): e145653.
pubmed: 34914636
pmcid: 8855822
doi: 10.1172/jci.insight.145653
Cheng X, Ji Z, Tsalkova T, Mei F. Epac and PKA: a tale of two intracellular cAMP receptors. Acta Biochim Biophys Sin (Shanghai). 2008;40(7):651–62.
pubmed: 18604457
doi: 10.1111/j.1745-7270.2008.00438.x
Lymperopoulos A, Borges JI, Stoicovy RA. Cyclic adenosine monophosphate in cardiac and sympathoadrenal GLP-1 receptor signaling: focus on anti-inflammatory effects. Pharmaceutics. 2024;16(6):693.
pubmed: 38931817
pmcid: 11206770
doi: 10.3390/pharmaceutics16060693
Vila Petroff MG, Egan JM, Wang X, Sollott SJ. Glucagon-like peptide-1 increases cAMP but fails to augment contraction in adult rat cardiac myocytes. Circ Res. 2001;89(5):445–52.
pubmed: 11532906
doi: 10.1161/hh1701.095716
Grammatika Pavlidou N, Dobrev S, Beneke K, Reinhardt F, Pecha S, Jacquet E, Abu-Taha IH, Schmidt C, Voigt N, Kamler M, Schnabel RB, Baczkó I, Garnier A, Reichenspurner H, Nikolaev VO, Dobrev D, Molina CE. Phosphodiesterase 8 governs cAMP/PKA-dependent reduction of L-type calcium current in human atrial fibrillation: a novel arrhythmogenic mechanism. Eur Heart J. 2023;44(27):2483–94.
pubmed: 36810794
pmcid: 10344654
doi: 10.1093/eurheartj/ehad086
Ang R, Mastitskaya S, Hosford PS, Basalay M, Specterman M, Aziz Q, Li Y, Orini M, Taggart P, Lambiase PD, Gourine A, Tinker A, Gourine AV. Modulation of cardiac ventricular excitability by GLP-1 (Glucagon-Like Peptide-1). Circ Arrhythm Electrophysiol. 2018;11(10): e006740.
pubmed: 30354404
pmcid: 6553567
doi: 10.1161/CIRCEP.118.006740
Sanin DE, Prendergast CT, Mountford AP. IL-10 Production in macrophages is regulated by a TLR-driven CREB-mediated mechanism that is linked to genes involved in cell metabolism. J Immunol. 2015;195(3):1218–32.
pubmed: 26116503
pmcid: 4505959
doi: 10.4049/jimmunol.1500146
Antonicelli F, De Coupade C, Russo-Marie F, Le Garrec Y. CREB is involved in mouse annexin A1 regulation by cAMP and glucocorticoids. Eur J Biochem. 2001;268(1):62–9.
pubmed: 11121103
doi: 10.1046/j.1432-1327.2001.01840.x
Gupta SC, Sundaram C, Reuter S, Aggarwal BB. Inhibiting NF-κB activation by small molecules as a therapeutic strategy. Biochim Biophys Acta. 2010;1799(10–12):775–87.
pubmed: 20493977
pmcid: 2955987
doi: 10.1016/j.bbagrm.2010.05.004
Lan YQ, Zhang C, Xiao JH, Zhuo YH, Guo H, Peng W, Ge J. Suppression of IkappaBalpha increases the expression of matrix metalloproteinase-2 in human ciliary muscle cells. Mol Vis. 2009;26(15):1977–87.
Takahashi N, Tetsuka T, Uranishi H, Okamoto T. Inhibition of the NF-kappaB transcriptional activity by protein kinase A. Eur J Biochem. 2002;269(18):4559–65.
pubmed: 12230568
doi: 10.1046/j.1432-1033.2002.03157.x
Christian F, Smith EL, Carmody RJ. The regulation of NF-κB subunits by phosphorylation. Cells. 2016;5(1):12.
pubmed: 26999213
pmcid: 4810097
doi: 10.3390/cells5010012
Gerlo S, Kooijman R, Beck IM, Kolmus K, Spooren A, Haegeman G. Cyclic AMP: a selective modulator of NF-κB action. Cell Mol Life Sci. 2011;68(23):3823–41. https://doi.org/10.1007/s00018-011-0757-8 .
doi: 10.1007/s00018-011-0757-8
pubmed: 21744067
pmcid: 11114830
Verma S, Poulter NR, Bhatt DL, Bain SC, Buse JB, Leiter LA, Nauck MA, Pratley RE, Zinman B, Ørsted DD, Monk Fries T, Rasmussen S, Marso SP. Effects of liraglutide on cardiovascular outcomes in patients with type 2 diabetes mellitus with or without history of myocardial infarction or stroke. Circulation. 2018;138(25):2884–94.
pubmed: 30566004
doi: 10.1161/CIRCULATIONAHA.118.034516
Noyan-Ashraf MH, Momen MA, Ban K, Sadi AM, Zhou YQ, Riazi AM, Baggio LL, Henkelman RM, Husain M, Drucker DJ. GLP-1R agonist liraglutide activates cytoprotective pathways and improves outcomes after experimental myocardial infarction in mice. Diabetes. 2009;58(4):975–83.
pubmed: 19151200
pmcid: 2661586
doi: 10.2337/db08-1193
Fang B, Liu F, Yu X, Luo J, Zhang X, Zhang T, Zhang J, Yang Y, Li X. Liraglutide alleviates myocardial ischemia-reperfusion injury in diabetic mice. Mol Cell Endocrinol. 2023;15(572): 111954.
doi: 10.1016/j.mce.2023.111954
Serraino GF, Jiritano F, Costa D, Ielapi N, Napolitano D, Mastroroberto P, Bracale UM, Andreucci M, Serra R. Metalloproteinases and hypertrophic cardiomyopathy: a systematic review. Biomolecules. 2023;13(4):665.
pubmed: 37189412
pmcid: 10136246
doi: 10.3390/biom13040665
Roldán V, Marín F, Gimeno JR, Ruiz-Espejo F, González J, Feliu E, García-Honrubia A, Saura D, de la Morena G, Valdés M, Vicente V. Matrix metalloproteinases and tissue remodeling in hypertrophic cardiomyopathy. Am Heart J. 2008;156(1):85–91.
pubmed: 18585501
doi: 10.1016/j.ahj.2008.01.035
Lymperopoulos A. Clinical pharmacology of cardiac cyclic AMP in human heart failure: too much or too little? Expert Rev Clin Pharmacol. 2023;16(7):623–30.
pubmed: 37403791
pmcid: 10529896
doi: 10.1080/17512433.2023.2233891
Huang H, Hong Q, Tan HL, Xiao CR, Gao Y. Ferulic acid prevents LPS-induced up-regulation of PDE4B and stimulates the cAMP/CREB signaling pathway in PC12 cells. Acta Pharmacol Sin. 2016;37(12):1543–54.
pubmed: 27665850
pmcid: 5260833
doi: 10.1038/aps.2016.88
Lugnier C. The complexity and multiplicity of the specific cAMP phosphodiesterase family: PDE4, open new adapted therapeutic approaches. Int J Mol Sci. 2022;23(18):10616.
pubmed: 36142518
pmcid: 9502408
doi: 10.3390/ijms231810616
Kranzler HR. Overview of alcohol use disorder. Am J Psychiatry. 2023;180(8):565–72.
pubmed: 37525595
doi: 10.1176/appi.ajp.20230488
Gutgesell RM, Nogueiras R, Tschöp MH, Müller TD. Dual and triple incretin-based co-agonists: novel therapeutics for obesity and diabetes. Diabetes Ther. 2024;15(5):1069–84.
pubmed: 38573467
pmcid: 11043266
doi: 10.1007/s13300-024-01566-x
Deng YW, Shu YG, Sun SL. miR-376a inhibits glioma proliferation and angiogenesis by regulating YAP1/VEGF signalling via targeting of SIRT1. Transl Oncol. 2022;15(1): 101270.
pubmed: 34808462
doi: 10.1016/j.tranon.2021.101270
Lymperopoulos A, Rengo G, Funakoshi H, Eckhart AD, Koch WJ. Adrenal GRK2 upregulation mediates sympathetic overdrive in heart failure. Nat Med. 2007;13(3):315–23.
pubmed: 17322894
doi: 10.1038/nm1553
Adnani L, Kassouf J, Meehan B, Spinelli C, Tawil N, Nakano I, Rak J. Angiocrine extracellular vesicles impose mesenchymal reprogramming upon proneural glioma stem cells. Nat Commun. 2022;13(1):5494.
pubmed: 36123372
pmcid: 9485157
doi: 10.1038/s41467-022-33235-7
Watanabe N, Tamai R, Kiyoura Y. Alendronate augments lipid A-induced IL-1β release by ASC-deficient RAW264 cells via AP-1 activation. Exp Ther Med. 2023;26(6):577.
pubmed: 38023354
pmcid: 10655061
doi: 10.3892/etm.2023.12276