The roles of PPARγ and its agonists in autoimmune diseases: A comprehensive review

Journal of Autoimmunity - Tập 113 - Trang 102510 - 2020
Yu Liu1, Jiayu Wang2, Shuang Luo1, Yi Zhan1, Qianjin Lu1
1Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenetics, Changsha, Hunan, 410011, PR China
2Xiangya Medical School, Central South University, #176 Tongzipo Rd, Changsha, Hunan, 410013, PR China

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Lu, 2014, Unmet needs in autoimmunity and potential new tools, Clin. Rev. Allergy Immunol., 47, 111, 10.1007/s12016-014-8414-2

Papp, 2017, Regulatory immune cells and functions in autoimmunity and transplantation immunology, Autoimmun. Rev., 16, 435, 10.1016/j.autrev.2017.03.011

Liu, 2014, TLR2 and TLR4 in autoimmune diseases: a comprehensive review, Clin. Rev. Allergy Immunol., 47, 136, 10.1007/s12016-013-8402-y

V, 2017, PPAR-gamma agonists as antineoplastic agents in cancers with dysregulated IGF Axis, Front. Endocrinol., 8, 31

Derosa, 2018, THE role of various peroxisome proliferator-activated receptors and their ligands in clinical practice, J. Cell. Physiol., 233, 10.1002/jcp.25804

Vallee, 2016, Alzheimer disease: crosstalk between the canonical wnt/beta-catenin pathway and PPARs alpha and gamma, Front. Neurosci., 10, 459, 10.3389/fnins.2016.00459

Corona, 2016, PPARgamma as a therapeutic target to rescue mitochondrial function in neurological disease, Free Radic. Biol. Med., 100, 153, 10.1016/j.freeradbiomed.2016.06.023

Kersten, 2017, The role and regulation of the peroxisome proliferator activated receptor alpha in human liver, Biochimie, 136, 75, 10.1016/j.biochi.2016.12.019

Chinetti-Gbaguidi, 2017, PPARbeta in macrophages and atherosclerosis, Biochimie, 136, 59, 10.1016/j.biochi.2016.12.008

Gupta, 2015, Peroxisome proliferator-activated receptors (PPARs) and PPAR agonists: the 'future' in dermatology therapeutics?, Arch. Dermatol. Res., 307, 767, 10.1007/s00403-015-1571-1

Kvandova, 2016, The role of PPARgamma in cardiovascular diseases, Physiol. Res., 65, S343, 10.33549/physiolres.933439

Griffiths, 2017, Redox regulation in metabolic programming and inflammation, Redox biology, 12, 50, 10.1016/j.redox.2017.01.023

Lamers, 2012, Therapeutic modulators of peroxisome proliferator-activated receptors (PPAR): a patent review (2008-present), Expert Opin. Ther. Pat., 22, 803, 10.1517/13543776.2012.699042

Scheen, 2015, Antidiabetic agents: potential anti-inflammatory activity beyond glucose control, Diabetes Metabol., 41, 183, 10.1016/j.diabet.2015.02.003

Kiss, 2013, The role of lipid-activated nuclear receptors in shaping macrophage and dendritic cell function: from physiology to pathology, J. Allergy Clin. Immunol., 132, 264, 10.1016/j.jaci.2013.05.044

Choi, 2012, The nuclear receptor PPARs as important regulators of T-cell functions and autoimmune diseases, Mol. Cell., 33, 217, 10.1007/s10059-012-2297-y

Garcia-Vallve, 2015, Peroxisome proliferator-activated receptor gamma (PPARgamma) and ligand choreography: newcomers take the stage, J. Med. Chem., 58, 5381, 10.1021/jm501155f

Naim, 2017, Therapeutic journey of 2,4-thiazolidinediones as a versatile scaffold: an insight into structure activity relationship, Eur. J. Med. Chem., 129, 218, 10.1016/j.ejmech.2017.02.031

Zoete, 2007, Peroxisome proliferator-activated receptor structures: ligand specificity, molecular switch and interactions with regulators, Biochim. Biophys. Acta, 1771, 915, 10.1016/j.bbalip.2007.01.007

Muralikumar, 2017, Probing the intermolecular interactions of PPARgamma-LBD with polyunsaturated fatty acids and their anti-inflammatory metabolites to infer most potential binding moieties, Lipids Health Dis., 16, 17, 10.1186/s12944-016-0404-3

Luo, 2016, Phytochemicals mediate the expression and activity of OCTN2 as activators of the PPARgamma/RXRalpha pathway, Front. Pharmacol., 7, 189, 10.3389/fphar.2016.00189

Grygiel-Gorniak, 2014, Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications–a review, Nutr. J., 13, 17, 10.1186/1475-2891-13-17

Chiu, 2017, Deciphering the roles of thiazolidinediones and PPARgamma in bladder cancer, PPAR Res., 2017, 4810672, 10.1155/2017/4810672

Wuertz, 2017, Thiazolidinediones abrogate cervical cancer growth, Exp. Cell Res., 353, 63, 10.1016/j.yexcr.2017.02.020

Tan, 2012, Novel transcriptome profiling analyses demonstrate that selective peroxisome proliferator-activated receptor gamma (PPARgamma) modulators display attenuated and selective gene regulatory activity in comparison with PPARgamma full agonists, Mol. Pharmacol., 82, 68, 10.1124/mol.111.076679

Bopst, 2017, Non-clinical safety evaluation and risk assessment to human of aleglitazar, a dual PPAR alpha/gamma agonist, and its major human metabolite, Regul. Toxicol. Pharmacol. : RTP (Regul. Toxicol. Pharmacol.), 86, 107, 10.1016/j.yrtph.2017.03.003

Kummer, 2015, Pan-PPAR modulation effectively protects APP/PS1 mice from amyloid deposition and cognitive deficits, Mol. Neurobiol., 51, 661, 10.1007/s12035-014-8743-4

Ferroni, 2013, Pleiotropic effects of PPARgamma agonist on hemostatic activation in type 2 diabetes mellitus, Curr. Vasc. Pharmacol., 11, 338, 10.2174/1570161111311030008

Chung, 2016, Nutrigenomic functions of PPARs in obesogenic environments, PPAR Res., 2016, 4794576, 10.1155/2016/4794576

Waku, 2009, Structural insight into PPARgamma activation through covalent modification with endogenous fatty acids, J. Mol. Biol., 385, 188, 10.1016/j.jmb.2008.10.039

Wang, 2014, Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARgamma): a review, Biochem. Pharmacol., 92, 73, 10.1016/j.bcp.2014.07.018

Sauer, 2015, Ligands for the nuclear peroxisome proliferator-activated receptor gamma, Trends Pharmacol. Sci., 36, 688, 10.1016/j.tips.2015.06.010

Dubois, 2017, Distinct but complementary contributions of PPAR isotypes to energy homeostasis, J. Clin. Invest., 127, 1202, 10.1172/JCI88894

Jung, 2017, Antidiabetic effect of SN158 through PPARalpha/gamma dual activation in ob/ob mice, Chem. Biol. Interact., 268, 24, 10.1016/j.cbi.2017.02.014

Bugge, 2017, PPAR agonists, - could tissue targeting pave the way?, Biochimie, 136, 100, 10.1016/j.biochi.2016.10.017

Henning, 2017, Consumption of a high-fat, high-calorie meal is associated with an increase in intracellular co-localization of PPAR-gamma mRNA and protein in monocytes, Methods (San Diego, Calif), 112, 182, 10.1016/j.ymeth.2016.07.007

Blanchard, 2016, Peroxisome proliferator-activated receptor gamma activation favours selective subcutaneous lipid deposition by coordinately regulating lipoprotein lipase modulators, fatty acid transporters and lipogenic enzymes, Acta Physiol., 217, 227, 10.1111/apha.12665

Holguin, 2007, The peroxisome proliferator activated receptor gamma (PPARgamma) ligand rosiglitazone modulates bronchoalveolar lavage levels of leptin, adiponectin, and inflammatory cytokines in lean and obese mice, Lung, 185, 367, 10.1007/s00408-007-9035-9

Baker, 2011, NF-kappaB, inflammation, and metabolic disease, Cell Metabol., 13, 11, 10.1016/j.cmet.2010.12.008

Y, 2020, Atorvastatin protects against postoperative neurocognitive disorder via a peroxisome proliferator-activated receptor-gamma signaling pathway in mice, J. Int. Med. Res., 48

S, 2020, Pioglitazone-mediated peroxisome proliferator-activated receptor γ activation aggravates murine immune-mediated hepatitis, Int. J. Mol. Sci., 21

M, 2020, Saroglitazar attenuates renal fibrosis induced by unilateral ureteral obstruction via inhibiting TGF-β/Smad signaling pathway, Life Sci., 253, 117729, 10.1016/j.lfs.2020.117729

Wang, 2017, Activation of PPARgamma inhibits pro-inflammatory cytokines production by upregulation of miR-124 in vitro and in vivo, Biochem. Biophys. Res. Commun., 486, 726, 10.1016/j.bbrc.2017.03.106

Yuan, 2016, PPARgamma inhibits HMGB1 expression through upregulation of miR-142-3p in vitro and in vivo, Cell. Signal., 28, 158, 10.1016/j.cellsig.2015.12.013

H, 2014, Ligand-activated peroxisome proliferator-activated receptor-δ and -γ inhibit lipopolysaccharide-primed release of high mobility group box 1 through upregulation of SIRT1, Cell Death Dis., 5, e1432, 10.1038/cddis.2014.406

Klotz, 2009, The nuclear receptor PPAR gamma selectively inhibits Th17 differentiation in a T cell-intrinsic fashion and suppresses CNS autoimmunity, J. Exp. Med., 206, 2079, 10.1084/jem.20082771

Xu, 2017, PPAR-gamma agonist ameliorates liver pathology accompanied by increasing regulatory B and T cells in high-fat-diet mice, Obesity, 25, 581, 10.1002/oby.21769

Nagy, 2012, Nuclear hormone receptors enable macrophages and dendritic cells to sense their lipid environment and shape their immune response, Physiol. Rev., 92, 739, 10.1152/physrev.00004.2011

Xia, 2017, Protectin DX increases survival in a mouse model of sepsis by ameliorating inflammation and modulating macrophage phenotype, Sci. Rep., 7, 99, 10.1038/s41598-017-00103-0

R, 2011, Autoimmune kidney disease and impaired engulfment of apoptotic cells in mice with macrophage peroxisome proliferator-activated receptor gamma or retinoid X receptor alpha deficiency, J. Immunol., 186, 621, 10.4049/jimmunol.1002230

A, 2020, Activation of PPAR-γ induces macrophage polarization and reduces neutrophil migration mediated by heme oxygenase 1, Int. Immunopharm., 84, 106565, 10.1016/j.intimp.2020.106565

L, 2016, Arctigenin suppress Th17 cells and ameliorates experimental autoimmune encephalomyelitis through AMPK and PPAR-γ/ROR-γt signaling, Mol. Neurobiol., 53, 5356, 10.1007/s12035-015-9462-1

Q, 2020, PPARγ-mediated microglial activation phenotype is involved in depressive-like behaviors and neuroinflammation in stressed C57BL/6J and ob/ob mice, Psychoneuroendocrinology, 117, 104674, 10.1016/j.psyneuen.2020.104674

C, 2020, Pharmacological (or synthetic) and nutritional agonists of PPAR-γ as candidates for cytokine storm modulation in COVID-19 disease, Molecules, 25

Lecarpentier, 2017, Interactions between PPAR gamma and the canonical wnt/beta-catenin pathway in type 2 diabetes and colon cancer, PPAR Res., 2017, 5879090, 10.1155/2017/5879090

Lecarpentier, 2017, Thermodynamics in cancers: opposing interactions between PPAR gamma and the canonical WNT/beta-catenin pathway, Clin. Transl. Med., 6, 14, 10.1186/s40169-017-0144-7

V, 2019, Hypothesis of opposite interplay between the canonical WNT/beta-catenin pathway and PPAR gamma in primary central nervous system lymphomas, Curr. Issues Mol. Biol., 31, 1

V, 2019, Targeting the canonical WNT/β-Catenin pathway in cancer treatment using non-steroidal anti-inflammatory drugs, Cells, 8

Kolkhir, 2017, Comorbidity of chronic spontaneous urticaria and autoimmune thyroid diseases: a systematic review, Allergy, 72, 10.1111/all.13182

Wang, 2017, The emerging role of epigenetics in autoimmune thyroid diseases, Front. Immunol., 8, 396

Mimura, 2003, Peroxisome proliferator-activated receptor-gamma gene expression in orbital adipose/connective tissues is increased during the active stage of Graves' ophthalmopathy, Thyroid : official journal of the American Thyroid Association, 13, 845, 10.1089/105072503322401032

Cheng, 2016, Celecoxib and pioglitazone as potential therapeutics for regulating TGF-beta-induced hyaluronan in dysthyroid myopathy, Invest. Ophthalmol. Vis. Sci., 57, 1951, 10.1167/iovs.15-18018

K, 2020, Anti-oxidative and anti-adipogenic effects of caffeine in an in vitro model of Graves' orbitopathy, Endocr. J., 67, 439, 10.1507/endocrj.EJ19-0521

Fallahi, 2016, Novel therapies for thyroid autoimmune diseases, Expet Rev. Clin. Pharmacol., 9, 853, 10.1586/17512433.2016.1157468

Werion, 2016, Pioglitazone, a PPARgamma agonist, upregulates the expression of caveolin-1 and catalase, essential for thyroid cell homeostasis: a clue to the pathogenesis of hashimoto's thyroiditis, Thyroid : official journal of the American Thyroid Association, 26, 1320, 10.1089/thy.2015.0625

F, 2019, Differential modulation of CXCL8 versus CXCL10, by cytokines, PPAR-gamma, or PPAR-alpha agonists, in primary cells from Graves' disease and ophthalmopathy, Autoimmun. Rev., 18, 673, 10.1016/j.autrev.2019.05.004

A, 2013, Interferon-α, -β and -γ induce CXCL11 secretion in human thyrocytes: modulation by peroxisome proliferator-activated receptor γ agonists, Immunobiology, 218, 690, 10.1016/j.imbio.2012.08.267

M, 2000, Peroxisome proliferator-activated receptor-gamma activators inhibit IFN-gamma-induced expression of the T cell-active CXC chemokines IP-10, Mig, and I-TAC in human endothelial cells, J. Immunol., 164, 6503, 10.4049/jimmunol.164.12.6503

D, 2019, CD70 defines a subset of proinflammatory and CNS-pathogenic T1/T17 lymphocytes and is overexpressed in multiple sclerosis, Cell. Mol. Immunol., 16, 652, 10.1038/s41423-018-0198-5

T, 2015, Association between vitamin D receptor polymorphisms and multiple sclerosis: systematic review and meta-analysis of case-control studies, Cell. Mol. Immunol., 12, 243, 10.1038/cmi.2014.47

Vallee, 2018, Demyelination in multiple sclerosis: reprogramming energy metabolism and potential PPARgamma agonist treatment approaches, Int. J. Mol. Sci., 19, 10.3390/ijms19041212

Natarajan, 2002, Peroxisome proliferator-activated receptor-gamma agonists inhibit experimental allergic encephalomyelitis by blocking IL-12 production, IL-12 signaling and Th1 differentiation, Gene Immun., 3, 59, 10.1038/sj.gene.6363832

Huang, 2011, Retinoid X receptor gamma signaling accelerates CNS remyelination, Nat. Neurosci., 14, 45, 10.1038/nn.2702

Giacoppo, 2015, An overview on neuroprotective effects of isothiocyanates for the treatment of neurodegenerative diseases, Fitoterapia, 106, 12, 10.1016/j.fitote.2015.08.001

Galuppo, 2014, Antiinflammatory activity of glucomoringin isothiocyanate in a mouse model of experimental autoimmune encephalomyelitis, Fitoterapia, 95, 160, 10.1016/j.fitote.2014.03.018

Giacoppo, 2016, Moringin activates Wnt canonical pathway by inhibiting GSK3beta in a mouse model of experimental autoimmune encephalomyelitis, Drug Des. Dev. Ther., 10, 3291, 10.2147/DDDT.S110514

Z, 2020, A dual effect of ursolic acid to the treatment of multiple sclerosis through both immunomodulation and direct remyelination, Proc. Natl. Acad. Sci. U.S.A., 117, 9082, 10.1073/pnas.2000208117

Racke, 2006, Nuclear receptors and autoimmune disease: the potential of PPAR agonists to treat multiple sclerosis, J. Nutr., 136, 700, 10.1093/jn/136.3.700

S, 2004, Anti-inflammatory and antiproliferative actions of PPAR-gamma agonists on T lymphocytes derived from MS patients, J. Leukoc. Biol., 75, 478, 10.1189/jlb.0803402

D, 2008, PPAR-gamma: therapeutic potential for multiple sclerosis, PPAR Res., 2008, 627463, 10.1155/2008/627463

Xu, 2007, Peroxisome proliferator-activated receptor-γ agonists suppress the production of IL-12 family cytokines by activated glia, J. Immunol., 178, 1904, 10.4049/jimmunol.178.3.1904

N, 2016, Immunologic effects of metformin and pioglitazone treatment on metabolic syndrome and multiple sclerosis, JAMA neurology, 73, 520, 10.1001/jamaneurol.2015.4807

Smolen, 2016, Rheumatoid arthritis, Lancet, 388, 2023, 10.1016/S0140-6736(16)30173-8

Leiming Zhang, 2017, Ginsenoside Rg1 attenuates adjuvant-induced arthritis in rats via modulation of PPAR-γ/NF-κB signal pathway, Oncotarget, 55384, 10.18632/oncotarget.19526

Pap, 2000, Modulation of fibroblast-mediated cartilage degradation by articular chondrocytes in rheumatoid arthritis, Arthritis Rheum., 43, 2531, 10.1002/1529-0131(200011)43:11<2531::AID-ANR21>3.0.CO;2-V

Marder, 2013, The peroxisome proliferator activated receptor-gamma pioglitazone improves vascular function and decreases disease activity in patients with rheumatoid arthritis, J Am Heart Assoc, 2, 10.1161/JAHA.113.000441

Li, 2017, Functional role of PPAR-gamma on the proliferation and migration of fibroblast-like synoviocytes in rheumatoid arthritis, Sci. Rep., 7, 12671, 10.1038/s41598-017-12570-6

Amasaki, 2002, Functional changes in rheumatoid fibroblast-like synovial cells through activation of peroxisome proliferator-activated receptor γ mediated signalling pathway, Clin. Exp. Immunol., 129, 379, 10.1046/j.1365-2249.2002.01876.x

Chung, 2008, Inflammation-associated insulin resistance: differential effects in rheumatoid arthritis and systemic lupus erythematosus define potential mechanisms, Arthritis Rheum., 58, 2105, 10.1002/art.23600

Shahin, 2010, Insulin resistance in early untreated rheumatoid arthritis patients, Clin. Biochem., 43, 661, 10.1016/j.clinbiochem.2010.01.012

Ormseth, 2013, Peroxisome proliferator-activated receptor γ agonist effect on rheumatoid arthritis: a randomized controlled trial, Arthritis Res. Ther., 15, 2, 10.1186/ar4290

Shahin, 2011, Effect of peroxisome proliferator-activated receptor gamma agonist (pioglitazone) and methotrexate on disease activity in rheumatoid arthritis (experimental and clinical study), Clin. Med. Insights Arthritis Musculoskelet. Disord., 4, 1, 10.4137/CMAMD.S5951

Avalos, 2007, Increased augmentation index in rheumatoid arthritis and its relationship to coronary artery atherosclerosis, J. Rheumatol., 34, 2388

Ormseth, 2014, Reversing vascular dysfunction in rheumatoid arthritis: improved augmentation index but not endothelial function with peroxisome proliferator-activated receptor gamma agonist therapy, Arthritis Rheum., 66, 2331, 10.1002/art.38686

X, 2019, 15-Deoxy-Δ-prostaglandin J as a potential regulator of bone metabolism via PPARγ-dependent and independent pathways: a review, Drug Des. Dev. Ther., 13, 1879, 10.2147/DDDT.S206695

A, 2019, The effect of ginger supplementation on some immunity and inflammation intermediate genes expression in patients with active Rheumatoid Arthritis, Gene, 698, 179, 10.1016/j.gene.2019.01.048

Y, 2018, Morin exerts anti-arthritic effects by attenuating synovial angiogenesis via activation of peroxisome proliferator activated receptor-γ, Mol. Nutr. Food Res., 62, e1800202, 10.1002/mnfr.201800202

Maria, 2017, Adipose-derived mesenchymal stem cells in autoimmune disorders: state of the art and perspectives for systemic sclerosis, Clin. Rev. Allergy Immunol., 52, 234, 10.1007/s12016-016-8552-9

Aringer, 2017, Recent advances in managing systemic sclerosis, F1000Research, 6, 88, 10.12688/f1000research.10022.1

Wei, 2011, Fibrosis in systemic sclerosis: emerging concepts and implications for targeted therapy, Autoimmun. Rev., 10, 267, 10.1016/j.autrev.2010.09.015

Dantas, 2015, The role of PPAR gamma in systemic sclerosis, PPAR Res., 2015, 124624, 10.1155/2015/124624

Ghosh, 2004, Disruption of transforming growth factor beta signaling and profibrotic responses in normal skin fibroblasts by peroxisome proliferator-activated receptor gamma, Arthritis Rheum., 50, 1305, 10.1002/art.20104

Kohno, 2006, Inhibition of skin sclerosis by 15deoxy delta12,14-prostaglandin J2 and retrovirally transfected prostaglandin D synthase in a mouse model of bleomycin-induced scleroderma, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 60, 18, 10.1016/j.biopha.2005.04.004

Wu, 2009, Rosiglitazone abrogates bleomycin-induced scleroderma and blocks profibrotic responses through peroxisome proliferator-activated receptor-gamma, Am. J. Pathol., 174, 519, 10.2353/ajpath.2009.080574

Kapoor, 2009, Loss of peroxisome proliferator-activated receptor gamma in mouse fibroblasts results in increased susceptibility to bleomycin-induced skin fibrosis, Arthritis Rheum., 60, 2822, 10.1002/art.24761

K, 2018, Adipocyte-specific repression of PPAR-gamma by NCoR contributes to scleroderma skin fibrosis, Arthritis Res. Ther., 20, 145, 10.1186/s13075-018-1630-z

Wei, 2010, PPARgamma downregulation by TGFss in fibroblast and impaired expression and function in systemic sclerosis: a novel mechanism for progressive fibrogenesis, PloS One, 5, e13778, 10.1371/journal.pone.0013778

Antonelli, 2013, Peroxisome proliferator-activated receptor gamma agonists reduce cell proliferation and viability and increase apoptosis in systemic sclerosis fibroblasts, Br. J. Dermatol., 168, 129, 10.1111/j.1365-2133.2012.11199.x

Lee, 2017, Deficient adipogenesis of scleroderma patient and healthy african American monocytes, Front. Pharmacol., 8, 174, 10.3389/fphar.2017.00174

Wei, 2012, Regulation of matrix remodeling by peroxisome proliferator-activated receptor-gamma: a novel link between metabolism and fibrogenesis, Open Rheumatol. J., 6, 103, 10.2174/1874312901206010103

Ameshima, 2003, Peroxisome proliferator-activated receptor gamma (PPARgamma) expression is decreased in pulmonary hypertension and affects endothelial cell growth, Circ. Res., 92, 1162, 10.1161/01.RES.0000073585.50092.14

Hansmann, 2008, An antiproliferative BMP-2/PPARγ/apoE axis in human and murine SMCs and its role in pulmonary hypertension, J. Clin. Invest., 118, 1846, 10.1172/JCI32503

Lopez-Isac, 2014, A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility, Arthritis Res. Ther., 16, R6, 10.1186/ar4432

Marangoni, 2015, A candidate gene study reveals association between a variant of the Peroxisome Proliferator-Activated Receptor Gamma (PPAR-gamma) gene and systemic sclerosis, Arthritis Res. Ther., 17, 128, 10.1186/s13075-015-0641-2

Wei, 2010, Peroxisome proliferator-activated receptor gamma: innate protection from excessive fibrogenesis and potential therapeutic target in systemic sclerosis, Curr. Opin. Rheumatol., 22, 671, 10.1097/BOR.0b013e32833de1a7

G-M, 2019, Cannabinoid derivatives acting as dual PPARγ/CB2 agonists as therapeutic agents for systemic sclerosis, Biochem. Pharmacol., 163, 321, 10.1016/j.bcp.2019.02.029

Gonzalez, 2012, Synthetic cannabinoid ajulemic acid exerts potent antifibrotic effects in experimental models of systemic sclerosis, Ann. Rheum. Dis., 71, 1545, 10.1136/annrheumdis-2011-200314

Lucattelli, 2016, Ajulemic acid exerts potent anti-fibrotic effect during the fibrogenic phase of bleomycin lung, Respir. Res., 17, 49, 10.1186/s12931-016-0373-0

Wei, 2014, A synthetic PPAR-gamma agonist triterpenoid ameliorates experimental fibrosis: PPAR-gamma-independent suppression of fibrotic responses, Ann. Rheum. Dis., 73, 446, 10.1136/annrheumdis-2012-202716

Ruzehaji, 2016, Pan PPAR agonist IVA337 is effective in prevention and treatment of experimental skin fibrosis, Ann. Rheum. Dis., 75, 2175, 10.1136/annrheumdis-2015-208029

Y, 2018, The therapeutic and pathogenic role of autophagy in autoimmune diseases, Front. Immunol., 9, 1512

L, 2018, A comprehensive review of immune-mediated dermatopathology in systemic lupus erythematosus, J. Autoimmun., 93, 1

Cannon, 2019, Tumour necrosis factor inhibitor exposure and radiographic outcomes in Veterans with rheumatoid arthritis: a longitudinal cohort study, Rheumatol Adv Pract, 3

O, 2011, PPARγ expression is increased in systemic lupus erythematosus patients and represses CD40/CD40L signaling pathway, Lupus, 20, 575, 10.1177/0961203310392419

Aprahamian, 2014, Peroxisome proliferator-activated receptor gamma agonists in the prevention and treatment of murine systemic lupus erythematosus, Immunology, 142, 363, 10.1111/imm.12256

Zhao, 2013, The peroxisome-proliferator activated receptor-gamma agonist pioglitazone modulates aberrant T cell responses in systemic lupus erythematosus, Clin. Immunol., 149, 119, 10.1016/j.clim.2013.07.002

Aprahamian, 2009, The peroxisome proliferator-activated receptor γ agonist rosiglitazone ameliorates murine lupus by induction of adiponectin, J. Immunol., 182, 340, 10.4049/jimmunol.182.1.340

Obreque, 2017, Autologous tolerogenic dendritic cells derived from monocytes of systemic lupus erythematosus patients and healthy donors show a stable and immunosuppressive phenotype, Immunology, 152, 648, 10.1111/imm.12806

A-S, 2018, Virgin olive oil and its phenol fraction modulate monocyte/macrophage functionality: a potential therapeutic strategy in the treatment of systemic lupus erythematosus, Br. J. Nutr., 120, 681, 10.1017/S0007114518001976

M, 2017, Immunomodulation in systemic lupus erythematosus: induction of M2 population in monocyte-derived macrophages by pioglitazone, Lupus, 26, 1318, 10.1177/0961203317701842

Z, 2020, Transitional B cells involved in autoimmunity and their impact on neuroimmunological diseases, J. Transl. Med., 18, 131, 10.1186/s12967-020-02289-w

B, 2020, Environmental factors in the pathogenesis of primary Sjögren’s syndrome, J. Intern. Med., 287

B, 2020, Sjogren-larsson syndrome: mechanisms and management, Appl. Clin. Genet., 13, 13, 10.2147/TACG.S193969

V, 2018, Impaired anti-inflammatory activity of PPARγ in the salivary epithelia of Sjögren's syndrome patients imposed by intrinsic NF-κB activation, J. Autoimmun., 86, 62, 10.1016/j.jaut.2017.09.007

B, 2003, Peroxisome proliferator-activated receptor agonists inhibit interleukin-1beta-mediated nitric oxide production in cultured lacrimal gland acinar cells, J. Ocul. Pharmacol. Therapeut. : the official journal of the Association for Ocular Pharmacology and Therapeutics, 19, 579, 10.1089/108076803322660495

L, 2014, Anti-inflammatory effect of peroxisome proliferator-activated receptor-γ (PPAR-γ) on non-obese diabetic mice with Sjogren's syndrome, Int. J. Clin. Exp. Pathol., 7, 4886

Katsiougiannis, 2019, Autoimmune epithelitis (Sjögren's syndrome); the impact of metabolic status of glandular epithelial cells on auto-immunogenicity, J. Autoimmun., 104, 102335, 10.1016/j.jaut.2019.102335

C, 2015, Primary biliary cirrhosis, Lancet (London, England), 386, 1565, 10.1016/S0140-6736(15)00154-3

F, 2015, Extrahepatic autoimmune conditions associated with primary biliary cirrhosis, Clin. Rev. Allergy Immunol., 48, 192, 10.1007/s12016-014-8427-x

N, 2013, PPARγ ligand attenuates portal inflammation in the MRL-lpr mouse: a new strategy to restrain cholangiopathy in primary biliary cirrhosis, Med. Mol. Morphol., 46, 153, 10.1007/s00795-013-0017-0

Corona, 2016, PPARγ as a therapeutic target to rescue mitochondrial function in neurological disease, Free Radic. Biol. Med., 100, 153, 10.1016/j.freeradbiomed.2016.06.023

Mirza, 2019, Role of PPAR receptor in different diseases and their ligands: physiological importance and clinical implications, Eur. J. Med. Chem., 166, 502, 10.1016/j.ejmech.2019.01.067

S, 2011, Effect of peroxisome proliferator-activated receptor gamma agonist (pioglitazone) and methotrexate on disease activity in rheumatoid arthritis (experimental and clinical study), Clin. Med. Insights Arthritis Musculoskelet. Disord., 4, 1

O, 2014, Reversing vascular dysfunction in rheumatoid arthritis: improved augmentation index but not endothelial function with peroxisome proliferator-activated receptor γ agonist therapy, Arthritis & rheumatology (Hoboken, NJ), 66, 2331

O, 2013, Peroxisome proliferator-activated receptor γ agonist effect on rheumatoid arthritis: a randomized controlled trial, Arthritis Res. Ther., 15, R110, 10.1186/ar4290

Krishnaswami, 2010, Thiazolidinediones: a 2010 perspective, Perm. J., 14, 64, 10.7812/TPP/09-052

Li, 2019, 15-Deoxy–(12,14)-Prostaglandin J2 (15d-PGJ2), an endogenous ligand of PPAR-gamma: function and mechanism, PPAR Res., 2019, 7242030, 10.1155/2019/7242030

A H, 2016, The effect of ω-fatty acids on mRNA expression level of PPARγ in patients with gastric adenocarcinoma, Exp. Oncol., 38, 191, 10.31768/2312-8852.2016.38(3):191-194

N, 2014, The role of nitrated fatty acids and peroxisome proliferator-activated receptor gamma in modulating inflammation, Int. Immunopharm., 23, 283, 10.1016/j.intimp.2014.09.009

Lamas Bervejillo, 2020, A FABP4-PPARγ signaling axis regulates human monocyte responses to electrophilic fatty acid nitroalkenes, Redox Biol, 29

Mateu, 2017, Oxidized phospholipids exert a dual effect on bile acid-induced CCL2 expression in pancreatic acini, Pancreatology, 17, 372, 10.1016/j.pan.2017.02.016

Plant, 2006, Amyloid beta peptide as a physiological modulator of neuronal 'A'-type K+ current, Neurobiol. Aging, 27, 1673, 10.1016/j.neurobiolaging.2005.09.038