Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Current Rheumatology Reports
Published in: Current Rheumatology Reports 6/2013

01-06-2013 | INFLAMMATORY MUSCLE DISEASE (I LUNDBERG, SECTION EDITOR)

The Role of Resistin in Inflammatory Myopathies

Authors: Mária Filková, Ladislav Šenolt, Jiří Vencovský

Published in: Current Rheumatology Reports | Issue 6/2013

Login to get access

Abstract

Both immune and non-immune mechanisms are involved in muscle damage and dysfunction occurring in idiopathic inflammatory myopathies (IIMs). Crosstalk among inflammatory cells, muscle and endothelial cells is essential in the pathogenesis of IIMs. Resistin, originally described as an adipokine linking obesity and insulin resistance in rodents, has been shown a pro-inflammatory molecule in humans. Besides its direct effect on production of several inflammatory mediators, resistin influences chemotaxis, migration, proliferation, cell survival, endothelial dysfunction and metabolism—all aspects implicated in the pathogenesis of IIMs. Up-regulation of resistin in muscle tissue and elevated serum resistin levels have been recently demonstrated in patients with IIMs. In addition, serum levels of resistin reflected global disease activity, including extramuscular organ involvement, in patients with this disease. However, there are currently not sufficient data to distinguish the features of resistin that cause injury of muscle tissue from those that promote muscle regeneration and repair. The aim of this review is therefore to summarize current knowledge about potential implication of resistin in idiopathic inflammatory myopathies.
Literature
1.
Lundberg IE, Grundtman C. Developments in the scientific and clinical understanding of inflammatory myopathies. Arthritis Res Ther. 2008;10:220.PubMedCrossRef
2.
Li CK, Knopp P, Moncrieffe H, et al. Overexpression of MHC class I heavy chain protein in young skeletal muscle leads to severe myositis: implications for juvenile myositis. Am J Pathol. 2009;175:1030–40.PubMedCrossRef
3.
•• Dalakas MC. Inflammatory muscle diseases: a critical review on pathogenesis and therapies. Curr Opin Pharmacol. 2010;10:346–52. Systematic review of the literature on the pathogenesis and management of inflammatory muscle diseases.PubMedCrossRef
4.
Figarella-Branger D, Civatte M, Bartoli C, et al. Cytokines, chemokines, and cell adhesion molecules in inflammatory myopathies. Muscle Nerve. 2003;28:659–82.PubMedCrossRef
5.
De Paepe B, Creus KK, De Bleecker JL. Role of cytokines and chemokines in idiopathic inflammatory myopathies. Curr Opin Rheumatol. 2009;21:610–6.PubMedCrossRef
6.
• Nasr R, Reed AM, Peterson EJ. Update: biomarkers for idiopathic inflammatory myopathies. Curr Opin Rheumatol. 2012;24:609–15. Systematic review of new biomarkers for idiopathic inflammatory myopathies.PubMed
7.
• Gómez R, Conde J, Scotece M, et al. What’s new in our understanding of the role of adipokines in rheumatic diseases? Nat Rev Rheumatol. 2011;7:528–36. Systematic review of the literature on the role of adipokines in rheumatic diseases.PubMedCrossRef
8.
Steppan CM, Bailey ST, Bhat S, et al. The hormone resistin links obesity to diabetes. Nature. 2001;409:307–12.PubMedCrossRef
9.
Filková M, Haluzík M, Gay S, et al. The role of resistin as a regulator of inflammation: implications for various human pathologies. Clin Immunol. 2009;133:157–70.PubMedCrossRef
10.
Savage DB, Sewter CP, Klenk ES, et al. Resistin / Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans. Diabetes. 2001;50:2199–202.PubMedCrossRef
11.
Lu SC, Shieh WY, Chen CY, et al. Lipopolysaccharide increases resistin gene expression in vivo and in vitro. FEBS Lett. 2002;530:158–62.PubMedCrossRef
12.
Anderson PD, Mehta NN, Wolfe ML, et al. Innate immunity modulates adipokines in humans. J Clin Endocrinol Metab. 2007;92:2272–9.PubMedCrossRef
13.
Lehrke M, Reilly MP, Millington SC, et al. An inflammatory cascade leading to hyperresistinemia in humans. PLoS Med. 2004;1:e45.PubMedCrossRef
14.
15.
Kaser S, Kaser A, Sandhofer A, et al. Resistin messenger-RNA expression is increased by proinflammatory cytokines in vitro. Biochem Biophys Res Commun. 2003;309:286–90.PubMedCrossRef
16.
Patel L, Buckels AC, Kinghorn IJ, et al. Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators. Biochem Biophys Res Commun. 2003;300:472–6.PubMedCrossRef
17.
Boström EA, Tarkowski A, Bokarewa M. Resistin is stored in neutrophil granules being released upon challenge with inflammatory stimuli. Biochim Biophys Acta. 2009;1793:1894–900.PubMedCrossRef
18.
Lee JH, Ort T, Ma K, et al. Resistin is elevated following traumatic joint injury and causes matrix degradation and release of inflammatory cytokines from articular cartilage in vitro. Osteoarthr Cartil. 2009;17:613–20.PubMedCrossRef
19.
• Zhang J, Lei T, Chen X, et al. Resistin up-regulates COX-2 expression via TAK1-IKK-NF-kappaB signaling pathway. Inflammation. 2010;33:25–33. Potential implication of resistin in inflammatory signaling pathways.PubMedCrossRef
20.
Bertolani C, Sancho-Bru P, Failli P, et al. Resistin as an intrahepatic cytokine: overexpression during chronic injury and induction of proinflammatory actions in hepatic stellate cells. J Pathol. 2006;169:2042–53.
21.
Son YM, Ahn SM, Kim GR, et al. Resistin enhances the expansion of regulatory T cells through modulation of dendritic cells. BMC Immunol. 2010;11:33.PubMedCrossRef
22.
Silswal N, Singh AK, Aruna B, et al. Human resistin stimulates the pro-inflammatory cytokines TNF-alpha and IL-12 in macrophages by NFkappaB-dependent pathway. Biochem Biophys Res Commun. 2005;334:1092–101.PubMedCrossRef
23.
Bokarewa M, Nagaev I, Dahlberg L, et al. Resistin, an adipokine with potent proinflammatory properties. J Immunol. 2005;174:5789–95.PubMed
24.
•• Tarkowski A, Bjersing J, Shestakov A, et al. Resistin competes with lipopolysaccharide for binding to toll-like receptor 4. J Cell Mol Med. 2010;14:1419–31. The original report demonstrating a receptor of resistin.PubMedCrossRef
25.
•• Filková M, Hulejová H, Kuncová K, et al. Resistin in idiopathic inflammatory myopathies. Arthritis Res Ther. 2012;14:R111. First report showing the role of resistin in idiopathic inflammatory myopathies.PubMedCrossRef
26.
Kim GT, Cho ML, Park YE, et al. Expression of TLR2, TLR4, and TLR9 in dermatomyositis and polymyositis. Clin Rheumatol. 2010;29:273–9.PubMedCrossRef
27.
Mackiewicz Z, Hukkanen M, Povilenaite D, et al. Dual effects of caspase-1, interleukin-1 beta, tumour necrosis factor-alpha and nerve growth factor receptor in inflammatory myopathies. Clin Exp Rheumatol. 2003;21:41–8.PubMed
28.
• Loell I, Lundberg IE. Can muscle regeneration fail in chronic inflammation: a weakness in inflammatory myopathies? J Intern Med. 2011;269:243–57. Summary of molecular and histopathological mechanisms standing behind muscle weakness in idiopathic inflammatory myopathies.PubMedCrossRef
29.
Kirman I, Vainer B, Nielsen OH. Interleukin-15 and ist role in chronic inflammatory diseases. Inflamm Res. 1998;47:285–9.PubMedCrossRef
30.
Busquets S, Figueras MT, Meijsing S, et al. Interleukin-15 decreases proteolysis in skeletalmuscle: a direct effect. Int J Mol Med. 2005;16:471–6.PubMed
31.
Kim M, Oh JK, Sakata S, et al. Role of resistin in cardiac contractility and hypertrophy. J Mol Cell Cardiol. 2008;45:270–80.PubMedCrossRef
32.
Kang S, Chemaly ER, Hajjar RJ, et al. Resistin promotes cardiac hypertrophy via the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) and c-Jun N-terminal kinase/insulin receptor substrate 1 (JNK/IRS1) pathways. J Biol Chem. 2011;286:18465–73.PubMedCrossRef
33.
Calabro P, Samudio I, Willerson JT, et al. Resistin promotes smooth muscle cell proliferation through activation of extracellular signal-regulated kinase 1/2 and phosphatidylinositol 3-kinase pathways. Circulation. 2004;110:3335–40.PubMedCrossRef
34.
Lawlor MA, Alessi DR. PKB/Akt: a key mediator of cell proliferation, survival and insulin responses? J Cell Sci. 2001;114:2903–10.PubMed
35.
Cohen G, Ilic D, Raupachova J, Hörl WH. Resistin inhibits essential functions of polymorphonuclear leukocytes. J Immunol. 2008;181:3761–8.PubMed
36.
Walcher D, Hess K, Berger R, et al. Resistin: a newly identified chemokine for human CD4-positive lymphocytes. Cardiovasc Res. 2010;85:167–74.PubMedCrossRef
37.
Jung HS, Park KH, Cho YM, et al. Resistin is secreted from macrophages in atheromas and promotes atherosclerosis. Cardiovasc Res. 2006;69:76–85.PubMedCrossRef
38.
Ding Q, Chai H, Mahmood N, et al. Matrix metalloproteinases modulated by protein kinase Cε mediate resistin-induced migration of human coronary artery smooth muscle cells. J Vasc Surg. 2011;53:1044–51.PubMedCrossRef
39.
Shyu KG, Lien LM, Wang BW, et al. Resistin contributes to neointimal formation via oxidative stress after vascular injury. Clin Sci (Lond). 2011;120:121–9.CrossRef
40.
Chakraborti S, Mandal M, Das S, et al. Regulation of matrix metalloproteinases: an overview. Mol Cell Biochem. 2003;253:269–85.PubMedCrossRef
41.
Mu H, Ohashi R, Yan S, et al. Adipokine resistin promotes in vitro angiogenesis of human endothelial cells. Cardiovasc Res. 2006;70:146–57.PubMedCrossRef
42.
Wu WT, Chen CN, Lin CI, et al. Lysophospholipids enhance matrix metalloproteinase-2 expression in human endothelial cells. Endocrinology. 2005;146:3387–400.PubMedCrossRef
43.
Verma S, Li SH, Wang CH, et al. Resistin promotes endothelial cell activation: further evidence of adipokine-endothelial interaction. Circulation. 2003;108:736–40.PubMedCrossRef
44.
Kawanami D, Maemura K, Takeda N, et al. Direct reciprocal effects of resistin and adiponectin on vascular endothelial cells: a new insight into adipocytokine-endothelial cell interactions. Biochem Biophys Res Commun. 2004;314:415–9.PubMedCrossRef
45.
Hung HF, Wang BW, Chang H, et al. The molecular regulation of resistin expression in cultured vascular smooth muscle cells under hypoxia. J Hypertens. 2008;26:2349–60.PubMedCrossRef
46.
•• Chemaly ER, Hadri L, Zhang S, et al. Long-term in vivo resistin overexpression induces myocardial dysfunction and remodeling in rats. J Mol Cell Cardiol. 2011;51:144–55. The role of resistin in multiple mechanisms of cell behaviour and organ homeostasis.PubMedCrossRef
47.
Chen C, Jiang J, Lü JM, et al. Resistin decreases expression of endothelial nitric oxide synthase through oxidative stress in human coronary artery endothelial cells. Am J Physiol Heart Circ Physiol. 2010;299:H193–201.PubMedCrossRef
48.
Park JH, Olsen NJ. Utility of magnetic resonance imaging in the evaluation of patients with inflammatory myopathies. Curr Rheumatol Rep. 2001;3:334–45.PubMedCrossRef
49.
Niederwanger A, Kranebitter M, Ciardi C, et al. Resistin impairs basal and insulin-induced glycogen synthesis by different mechanisms. Mol Cell Endocrinol. 2007;263:112–9.PubMedCrossRef
50.
Palanivel R, Maida A, Liu Y, et al. Regulation of insulin signalling, glucose uptake and metabolism in rat skeletal muscle cells upon prolonged exposure to resistin. Diabetologia. 2006;49:183–90.PubMedCrossRef
51.
Jørgensen SB, Honeyman J, Oakhill JS, et al. Oligomeric resistin impairs insulin and AICAR-stimulated glucose uptake in mouse skeletal muscle by inhibiting GLUT4 translocation. Am J Physiol Endocrinol Metab. 2009;297:E57–66.PubMedCrossRef
52.
Fan HQ, Gu N, Liu F, et al. Prolonged exposure to resistin inhibits glucose uptake in rat skeletal muscles. Acta Pharmacol Sin. 2007;28:410–6.PubMedCrossRef
53.
Moon B, Kwan JJ, Duddy N, et al. Resistin inhibits glucose uptake in L6 cells independently of changes in insulin signaling and GLUT4 translocation. Am J Physiol Endocrinol Metab. 2003;285:E106–15.PubMed
54.
Schaffler A, Ehling A, Neumann E, et al. Adipocytokines in synovial fluid. JAMA. 2003;290:1709–10.PubMedCrossRef
55.
Senolt L, Housa D, Vernerová Z, et al. Resistin in rheumatoid arthritis synovial tissue, synovial fluid and serum. Ann Rheum Dis. 2007;66:458–63.PubMedCrossRef
56.
Migita K, Maeda Y, Miyashita T, et al. The serum levels of resistin in rheumatoid arthritis patients. Clin Exp Rheumatol. 2006;24:698–701.PubMed
57.
Forsblad d'Elia H, Pullerits R, Carlsten H, et al. Resistin in serum is associated with higher levels of IL-1Ra in post-menopausal women with rheumatoid arthritis. Rheumatology (Oxford). 2008;47:1082–7.CrossRef
58.
Avouac J, Allanore Y. Cardiovascular risk in rheumatoid arthritis: effects of anti-TNF drugs. Expert Opin Pharmacother. 2008;9:1121–8.PubMedCrossRef
59.
Gonzalez-Gay MA, Garcia-Unzueta MT, Gonzalez-Juanatey C, et al. Anti-TNF-alpha therapy modulates resistin in patients with rheumatoid arthritis. Clin Exp Rheumatol. 2008;26:311–6.PubMed
60.
Klaasen R, Herenius MM, Wijbrandts CA, et al. Treatment-specific changes in circulating adipocytokines: a comparison between tumour necrosis factor blockade and glucocorticoid treatment for rheumatoid arthritis. Ann Rheum Dis. 2012;71:1510–6.PubMedCrossRef
61.
Almehed K, d'Elia HF, Bokarewa M, et al. Role of resistin as a marker of inflammation in systemic lupus erythematosus. Arthritis Res Ther. 2008;10:R15.PubMedCrossRef
62.
Boström EA, d'Elia HF, Dahlgren U, et al. Salivary resistin reflects local inflammation in Sjögren’s syndrome. J Rheumatol. 2008;35(10):2005–11.PubMed
63.
Johnston A, Arnadottir S, Gudjonsson JE, et al. Obesity in psoriasis: leptin and resistin as mediators of cutaneous inflammation. Br J Dermatol. 2008;159:342–50.PubMedCrossRef
64.
Corbetta S, Angioni R, Cattaneo A, et al. Effects of retinoid therapy on insulin sensitivity, lipid profile and circulating adipocytokines. Eur J Endocrinol. 2006;154:83–6.PubMedCrossRef
65.
Kocabas H, Kocabas V, Buyukbas S, et al. The serum levels of resistin in ankylosing spondylitis patients: a pilot study. Rheumatol Int. 2012;32:699–702.PubMedCrossRef
66.
Hulejová H, Levitová A, Kuklová M, et al. No effect of physiotherapy on the serum levels of adipocytokines in patients with ankylosing spondylitis. Clin Rheumatol. 2012;31:67–71.PubMedCrossRef
67.
Pehlivan Y, Onat AM, Ceylan N, et al. Serum leptin, resistin and TNF-α levels in patients with systemic sclerosis: the role of adipokines in scleroderma. Int J Rheum Dis. 2012;15:374–9.PubMedCrossRef
68.
Gheita TA, El-Gazzar II, El Shazly RI, et al. Elevated serum resistin in juvenile idiopathicarthritis: relation to categories and disease activity. J Clin Immunol. 2012 Aug 11. [Epub ahead of print].
69.
• Boström EA, Ekstedt M, Kechagias S, et al. Resistin is associated with breach of tolerance and anti-nuclear antibodies in patients with hepatobiliary inflammation. Scand J Immunol. 2011;74:463–70. Association between resistin and autoantibodies in inflammatory diseases.PubMedCrossRef
70.
Isenberg DA, Allen E, Farewell V, et al. International consensus outcome measures for patients with idiopathic inflammatory myopathies. Development and initial validation of myositis activity and damage indices in patients with adult onset disease. Rheumatology (Oxford). 2004;43(1):49–54.CrossRef
71.
Lundberg IE. New possibilities to achieve increased understanding of disease mechanisms in idiopathic inflammatory myopathies. Curr Opin Rheumatol. 2002;14:639–42.PubMedCrossRef
Metadata
Title
The Role of Resistin in Inflammatory Myopathies
Authors
Mária Filková
Ladislav Šenolt
Jiří Vencovský
Publication date
01-06-2013
Publisher
Current Science Inc.
Published in
Current Rheumatology Reports / Issue 6/2013
Print ISSN: 1523-3774
Electronic ISSN: 1534-6307
DOI
https://doi.org/10.1007/s11926-013-0336-0

Other articles of this Issue 6/2013

Current Rheumatology Reports 6/2013 Go to the issue

OSTEOARTHRITIS (MB GOLDRING, SECTION EDITOR)

Understanding Developmental Mechanisms in the Context of Osteoarthritis

INFLAMMATORY MUSCLE DISEASE (I LUNDBERG, SECTION EDITOR)

Autoantibodies in Polymyositis and Dermatomyositis

INFECTIONS AND ARTHRITIS (K WINTHROP, SECTION EDITOR)

Vaccination and Inflammatory Arthritis: Overview of Current Vaccines and Recommended Uses in Rheumatology

SYSTEMIC LUPUS ERYTHEMATOSUS (M PETRI, SECTION EDITOR)

Top 10 Things to Know About Lupus Activity Measures

INFECTIONS AND ARTHRITIS (K WINTHROP, SECTION EDITOR)

Clinical Management of Septic Arthritis

ANTIPHOSPHOLIPID SYNDROME (RAS ROUBEY, SECTION EDITOR)

Use of New Oral Anticoagulants in Antiphospholipid Syndrome
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits