Accelerated, severe lupus nephritis benefits from treatment with honokiol by immunoregulation and differentially regulating NF-κB/NLRP3 inflammasome and sirtuin 1/autophagy axis.
Animals
Anti-Inflammatory Agents
/ therapeutic use
Autophagy
Biphenyl Compounds
/ therapeutic use
Cells, Cultured
Female
Inflammasomes
/ drug effects
Kidney
/ drug effects
Lignans
/ therapeutic use
Lupus Nephritis
/ drug therapy
Mice
NF-kappa B
/ metabolism
NLR Family, Pyrin Domain-Containing 3 Protein
/ metabolism
Reactive Oxygen Species
/ metabolism
Sirtuin 1
/ metabolism
T-Lymphocytes
/ drug effects
NLRP3 inflammasome
accelerated
autophagy
honokiol
severe lupus nephritis
sirtuin 1
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
28
05
2020
revised:
08
07
2020
accepted:
16
07
2020
pubmed:
20
8
2020
medline:
1
5
2021
entrez:
20
8
2020
Statut:
ppublish
Résumé
Using honokiol (HNK), a major anti-inflammatory bioactive compound in Magnolia officinalis, we show a potent therapeutic outcome against an accelerated, severe form of lupus nephritis (ASLN). The latter may follow infectious insults that act as environmental triggers in the patients. In the current study, an ASLN model in NZB/W F1 mice was treated with HNK by daily gavage after onset of the disease. We show that HNK ameliorated the ASLN by improving renal function, albuminuria, and renal pathology, especially reducing cellular crescents, neutrophil influx, fibrinoid necrosis in glomeruli, and glomerulonephritis activity scores. Meanwhile, HNK differentially regulated T cell functions, reduced serum anti-dsDNA autoantibodies, and inhibited NLRP3 inflammasome activation in the mice. The latter involved: (a) suppressed production of reactive oxygen species and NF-κB activation-mediated priming signal of the inflammasome, (b) reduced mitochondrial damage, and (c) enhanced sirtuin 1 (SIRT1)/autophagy axis activation. In conclusion, HNK represents a new drug candidate for acute, severe episodes of LN capable of alleviating renal lesions in ASLN mice by negatively regulating T cell functions and by enhancing SIRT1/autophagy axis-lessened NLRP3 inflammasome activation.
Identifiants
pubmed: 32813287
doi: 10.1096/fj.202001326R
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Biphenyl Compounds
0
Inflammasomes
0
Lignans
0
NF-kappa B
0
NLR Family, Pyrin Domain-Containing 3 Protein
0
Nlrp3 protein, mouse
0
Reactive Oxygen Species
0
honokiol
11513CCO0N
Sirt1 protein, mouse
EC 3.5.1.-
Sirtuin 1
EC 3.5.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
13284-13299Informations de copyright
© 2020 Federation of American Societies for Experimental Biology.
Références
Whittall-García L, Torres-Ruiz J, Zentella-Dehesa A, et al. Neutrophil extracellular traps are a source of extracellular HMGB1 in lupus nephritis: associations with clinical and histopathological features. Lupus. 2019;28:1549-1557.
Ayyappan P, Harms RZ, Buckner JH, Sarvetnick NE. Coordinated induction of antimicrobial response factors in systemic lupus erythematosus. Front Immunol. 2019;10:658.
Kronbichler A, Kerschbaum J, Mayer, G. The influence and role of microbial factors in autoimmune kidney diseases: a systematic review. J Immunol Res. 2015;2015:1-13.
Weening JJ, D’Agati VD, Schwartz MM, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol. 2004;15:241-250.
Mittal B, Hurwitz S, Rennke H, Singh AK. New subcategories of class IV lupus nephritis: are there clinical, histologic, and outcome differences? Am J Kidney Dis. 2004;44:1050-1059.
Tucci M, Stucci S, Strippoli S, Silvestris F. Cytokine overproduction, T-cell activation, and defective T-regulatory functions promote nephritis in systemic lupus erythematosus. Biomed Res Int. 2010;2010:457146.
Haas KM, Watanabe R, Matsushita T, et al. Protective and pathogenic roles for B cells during systemic autoimmunity in NZB/W F1 mice. J Immunol. 2010;184:4789-4800.
Yang S-R, Hua K-F, Chu LJ, et al. Xenon blunts NF-κB/NLRP3 inflammasome activation and improves acute onset of accelerated and severe lupus nephritis in mice. Kidney Int. 2020;98(2):378-390.
Lin T-J, Wu C-Y, Tsai P-Y, et al. Accelerated and severe lupus nephritis benefits from M1, an active metabolite of ginsenoside, by regulating NLRP3 inflammasome and T cell functions in mice. Front Immunol. 2019;10:1951.
Ka S-M, Lin J-C, Lin T-J, et al. Citral alleviates an accelerated and severe lupus nephritis model by inhibiting the activation signal of NLRP3 inflammasome and enhancing Nrf2 activation. Arthritis Res Ther. 2015;17:331.
Tsai PY, Ka SM, Chang JM, et al. Antroquinonol differentially modulates T cell activity and reduces interleukin-18 production, but enhances Nrf2 activation, in murine accelerated severe lupus nephritis. Arthritis Rheum. 2012;64:232-242.
Benseler S, Bargman J, Feldman B, et al. Acute renal failure in paediatric systemic lupus erythematosus: treatment and outcome. Rheumatology. 2009;48:176-182.
Molino C, Fabbian F, Longhini C. Clinical approach to lupus nephritis: recent advances. Eur J Intern Med. 2009;20:447-453.
Illei GG, Austin HA, Crane M, et al. Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis. Ann Intern Med. 2001;135:248-257.
Flanc RS, Roberts MA, Strippoli GF, Chadban SJ, Kerr PG, Atkins RC. Treatment of diffuse proliferative lupus nephritis: a meta-analysis of randomized controlled trials. Am J Kidney Dis. 2004;43:197-208.
Watanabe K, Watanabe H, Goto Y, Yamaguchi M, Yamamoto N, Hagino K. Pharmacological properties of magnolol and hōnokiol extracted from Magnolia officinalis: central depressant effects. Planta Med. 1983;49:103-108.
Squires RF, Ai J, Witt M-R, et al. Honokiol and magnolol increase the number of [3 H] muscimol binding sites three-fold in rat forebrain membranes in vitro using a filtration assay, by allosterically increasing the affinities of low-affinity sites. Neurochem Res. 1999;24:1593-1602.
Chao LK, Liao P-C, Ho C-L, et al. Anti-inflammatory bioactivities of honokiol through inhibition of protein kinase C, mitogen-activated protein kinase, and the NF-κB pathway to reduce LPS-induced TNFα and NO expression. J Agric Food Chem. 2010;58:3472-3478.
Li CY, Chao LK, Wang SC, et al. Honokiol inhibits LPS-induced maturation and inflammatory response of human monocyte-derived dendritic cells. J Cell Physiol. 2011;226:2338-2349.
Pillai VB, Kanwal A, Fang YH, et al. Honokiol, an activator of Sirtuin-3 (SIRT3) preserves mitochondria and protects the heart from doxorubicin-induced cardiomyopathy in mice. Oncotarget. 2017;8:34082-34098.
Huang PP, Fu J, Liu LH, et al. Honokiol antagonizes doxorubicin-induced cardiomyocyte senescence by inhibiting TXNIP-mediated NLRP3 inflammasome activation. Int J Mol Med. 2020;45:186-194.
Guo N, Liu Z, Yan Z, et al. Subinhibitory concentrations of Honokiol reduce α-Hemolysin (Hla) secretion by Staphylococcus aureus and the Hla-induced inflammatory response by inactivating the NLRP3 inflammasome. Emerg Microbes Infect. 2019;8:707-716.
Tsai P-Y, Ka S-M, Chang J-M, et al. Epigallocatechin-3-gallate prevents lupus nephritis development in mice via enhancing the Nrf2 antioxidant pathway and inhibiting NLRP3 inflammasome activation. Free Radic Biol Med. 2011;51:744-754.
Kahlenberg JM, Kaplan MJ. The inflammasome and lupus-another innate immune mechanism contributing to disease pathogenesis? Curr Opin Rheumatol. 2014;26:475-481.
Zhao J, Wang H, Huang Y, et al. Lupus nephritis: glycogen synthase kinase 3β promotion of renal damage through activation of the NLRP3 inflammasome in lupus-prone mice. Arthritis Rheumatol. 2015;67:1036-1044.
Fu R, Guo C, Wang S, et al. Podocyte activation of NLRP3 inflammasomes contributes to the development of proteinuria in lupus nephritis. Arthritis Rheumatol. 2017;69:1636-1646.
Li X, Wang M, Hong H, Luo C, Liu Z, Yang R. Sophocarpine attenuates murine lupus nephritis via inhibiting NLRP3 inflammasome and NF-κB activation. Immunol Res. 2018;66:521-527.
Clarke AJ, Ellinghaus U, Cortini A, et al. Autophagy is activated in systemic lupus erythematosus and required for plasmablast development. Ann Rheum Dis. 2015;74:912-920.
Wang L, Law H. The role of autophagy in lupus nephritis. Int J Mol Sci. 2015;16:25154-25167.
Harris J, Hartman M, Roche C, et al. Autophagy controls IL-1β secretion by targeting pro-IL-1β for degradation. J Biol Chem. 2011;286:9587-9597.
Ko JH, Yoon S-O, Lee HJ, Oh JY. Rapamycin regulates macrophage activation by inhibiting NLRP3 inflammasome-p38 MAPK-NFκB pathways in autophagy-and p62-dependent manners. Oncotarget. 2017;8:40817-40831.
Lee IH, Cao L, Mostoslavsky R, et al. A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc Natl Acad Sci. 2008;105:3374-3379.
Hariharan N, Maejima Y, Nakae J, Paik J, DePinho RA, Sadoshima J. Deacetylation of FoxO by Sirt1 plays an essential role in mediating starvation-induced autophagy in cardiac myocytes. Circ Res. 2010;107:1470-1482.
Danz EDB, Skramsted J, Henry N, Bennett JA, Keller RS. Resveratrol prevents doxorubicin cardiotoxicity through mitochondrial stabilization and the Sirt1 pathway. Free Radic Biol Med. 2009;46:1589-1597.
Fu Y, Wang Y, Du L, et al. Resveratrol inhibits ionising irradiation-induced inflammation in MSCs by activating SIRT1 and limiting NLRP-3 inflammasome activation. Int J Mol Sci. 2013;14:14105-14118.
He Q, Li Z, Wang Y, Hou Y, Li L, Zhao J. Resveratrol alleviates cerebral ischemia/reperfusion injury in rats by inhibiting NLRP3 inflammasome activation through Sirt1-dependent autophagy induction. Int Immunopharmacol. 2017;50:208-215.
Cavallo T, Granholm N. Accelerated (proliferative) lupus nephritis. Am J Pathol. 1990;137:1549.
Cavallo T, Granholm N. Bacterial lipopolysaccharide transforms mesangial into proliferative lupus nephritis without interfering with processing of pathogenic immune complexes in NZB/W mice. Am J Pathol. 1990;137:971.
Tsai P-Y, Ka S-M, Chang J-M, et al. Therapeutic potential of DCB-SLE1, an extract of a mixture of Chinese medicinal herbs, for severe lupus nephritis. Am J Physiol-Renal Physiol. 2011;301:F751-F764.
Chen A, Sheu L-F, Ho Y-S, et al. Experimental focal segmental glomerulosclerosis in mice. Nephron. 1998;78:440-452.
Ka S-M, Sytwu H-K, Chang D-M, Hsieh S-L, Tsai P-Y, Chen A. Decoy receptor 3 ameliorates an autoimmune crescentic glomerulonephritis model in mice. J Am Soc Nephrol. 2007;18:2473-2485.
Chen A, Lai-Fa S, Wei-Yuan C, et al. Interleukin-1 receptor antagonist modulates the progression of a spontaneously occurring IgA nephropathy in mice. Am J Kidney Dis. 1997;30:693-702.
Ka S-M, Rifai A, Chen J-H, et al. Glomerular crescent-related biomarkers in a murine model of chronic graft versus host disease. Nephrol Dial Transplant. 2005;21:288-298.
Ka S, Yeh Y, Huang X, et al. Kidney-targeting Smad7 gene transfer inhibits renal TGF-β/MAD homologue (SMAD) and nuclear factor κB (NF-κB) signalling pathways, and improves diabetic nephropathy in mice. Diabetologia. 2012;55:509-519.
Wu CY, Hua KF, Chu CL, et al. Tris DBA ameliorates accelerated and severe lupus nephritis in mice by activating regulatory T cells and autophagy and inhibiting the NLRP3 inflammasome. J Immunol. 2020;204:1448-1461.
Chang YP, Ka SM, Hsu WH, et al. Resveratrol inhibits NLRP3 inflammasome activation by preserving mitochondrial integrity and augmenting autophagy. J Cell Physiol. 2015;230:1567-1579.
Chiu H-W, Li L-H, Hsieh C-Y, et al. Glucosamine inhibits IL-1β expression by preserving mitochondrial integrity and disrupting assembly of the NLRP3 inflammasome. Sci Rep. 2019;9(1):5603.
Kelley N, Jeltema D, Duan Y, He Y. The NLRP3 inflammasome: an overview of mechanisms of activation and regulation. Int J Mol Sci. 2019;20:3328.
Muñoz-Planillo R, Kuffa P, Martínez-Colón G, Smith BL, Rajendiran TM, Núñez G. K+ efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity. 2013;38:1142-1153.
Tang T, Lang X, Xu C, et al. CLICs-dependent chloride efflux is an essential and proximal upstream event for NLRP3 inflammasome activation. Nat Commun. 2017;8:202.
Groß CJ, Mishra R, Schneider KS, et al. K+ efflux-independent NLRP3 inflammasome activation by small molecules targeting mitochondria. Immunity. 2016;45:761-773.
Kepp O, Galluzzi L, Kroemer G. Mitochondrial control of the NLRP3 inflammasome. Nat Immunol. 2011;12:199-200.
Liao P-C, Chao LK, Chou J-C, et al. Lipopolysaccharide/adenosine triphosphate-mediated signal transduction in the regulation of NLRP3 protein expression and caspase-1-mediated interleukin-1β secretion. Inflamm Res. 2013;62:89-96.
Park S-H, Ham S, Lee A, Möller A, Kim TS. NLRP3 negatively regulates Treg differentiation through Kpna2-mediated nuclear translocation. J Biol Chem. 2019;294:17951-17961.
Arbore G, West EE, Spolski R, et al. T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4+ T cells. Science. 2016;352:aad1210.
Meng G, Zhang F, Fuss I, Kitani A, Strober W. A mutation in the Nlrp3 gene causing inflammasome hyperactivation potentiates Th17 cell-dominant immune responses. Immunity. 2009;30:860-874.
Gris D, Ye Z, Iocca HA, et al. NLRP3 plays a critical role in the development of experimental autoimmune encephalomyelitis by mediating Th1 and Th17 responses. J Immunol. 2010;185:974-981.
Bruchard M, Rebé C, Derangère V, et al. The receptor NLRP3 is a transcriptional regulator of TH 2 differentiation. Nat Immunol. 2015;16:859-870.
Shin MS, Kang Y, Lee N, et al. Self double-stranded (ds) DNA induces IL-1β production from human monocytes by activating NLRP3 inflammasome in the presence of anti-dsDNA antibodies. J Immunol. 2013;190:1407-1415.
Zhang H, Fu R, Guo C, et al. Anti-dsDNA antibodies bind to TLR4 and activate NLRP3 inflammasome in lupus monocytes/macrophages. J Transl Med. 2016;14:156.
Fernandes-Alnemri T, Yu J-W, Datta P, Wu J, Alnemri ES. AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature. 2009;458:509-513.
Akhtar S, Li X, Kovacs EJ, Gamelli RL, Choudhry MA. Interleukin-18 delays neutrophil apoptosis following alcohol intoxication and burn injury. Mol Med. 2011;17:88-94.
Costantini C, Micheletti A, Calzetti F, Perbellini O, Pizzolo G, Cassatella MA. Neutrophil activation and survival are modulated by interaction with NK cells. Int Immunol. 2010;22:827-838.