nach oben

Journal of Clinical Immunology

Erschienen in:

01.04.2011

Modulation of Lupus Phenotype by Adiponectin Deficiency in Autoimmune Mouse Models

verfasst von: Jennifer Parker, Hanni Menn-Josephy, Bari Laskow, Yukihiro Takemura, Tamar Aprahamian

Erschienen in: Journal of Clinical Immunology | Ausgabe 2/2011

Einloggen, um Zugang zu erhalten

Abstract

Adiponectin is an adipocyte-derived cytokine with anti-inflammatory properties. Paradoxically, circulating adiponectin levels are increased in a number of inflammatory diseases. Thus, we sought to define the role of adiponectin deficiency in mouse models of autoimmunity. Adiponectin-deficient mice on a C57BL/6 background do not develop an autoimmune phenotype. Autoimmunity was also not observed in adiponectin-deficient mice generated on the permissive MRL background. However, adiponectin deficiency exacerbated the autoimmune phenotype of MRL-lpr mice. Compared with MRL-lpr mice, MRL-lpr.apn^−/− mice displayed greater lymphadenopathy and splenomegaly, as well as increased anti-nuclear antibody and anti-dsDNA production. In addition, evaluation of the kidney revealed larger glomerular tuft size, crescent formation, increased IgG and C3 deposits, and mesangial expansion in the MRL-lpr.apn^−/− mice. The effects of adiponectin deficiency on the autoimmune phenotypes were more pronounced in female versus male mice. These data show that, while adiponectin deficiency is not sufficient to confer autoimmunity, adiponectin acts as a negative modulator of the autoimmune phenotype in a murine model of lupus.

Berg AH, Scherer PE. Adipose tissue, inflammation, and cardiovascular disease. Circ Res. 2005;96:939–49.PubMedCrossRef

Ouchi N, Kihara S, Funahashi T, Matsuzawa Y, Walsh K. Obesity, adiponectin and vascular inflammatory disease. Curr Opin Lipidol. 2003;14:561–6.PubMedCrossRef

Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 1999;257:79–83.PubMedCrossRef

Ryo M, Nakamura T, Kihara S, Kumada M, Shibazaki S, Takahashi M, et al. Adiponectin as a biomarker of the metabolic syndrome. Circ J. 2004;68:975–81.PubMedCrossRef

Fasshauer M, Kralisch S, Klier M, Lossner U, Bluher M, Klein J, et al. Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes. Biochem Biophys Res Commun. 2003;301:1045–50.PubMedCrossRef

Kappes A, Loffler G. Influences of ionomycin, dibutyryl-cycloAMP and tumour necrosis factor-alpha on intracellular amount and secretion of apM1 in differentiating primary human preadipocytes. Horm Metab Res. 2000;32:548–54.PubMedCrossRef

Maeda N, Takahashi M, Funahashi T, Kihara S, Nishizawa H, Kishida K, et al. PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes. 2001;50:2094–9.PubMedCrossRef

Isobe T, Saitoh S, Takagi S, Takeuchi H, Chiba Y, Katoh N, et al. Influence of gender, age and renal function on plasma adiponectin level: the Tanno and Sobetsu study. Eur J Endocrinol. 2005;153:91–8.PubMedCrossRef

Spranger J, Kroke A, Mohlig M, Bergmann MM, Ristow M, Boeing H, et al. Adiponectin and protection against type 2 diabetes mellitus. Lancet. 2003;361:226–8.PubMedCrossRef

10.

Iwashima Y, Horio T, Kumada M, Suzuki Y, Kihara S, Rakugi H, et al. Adiponectin and renal function, and implication as a risk of cardiovascular disease. Am J Cardiol. 2006;98:1603–8.PubMedCrossRef

11.

Pischon T, Girman CJ, Hotamisligil GS, Rifai N, Hu FB, Rimm EB. Plasma adiponectin levels and risk of myocardial infarction in men. JAMA. 2004;291:1730–7.PubMedCrossRef

12.

Atzmon G, Pollin TI, Crandall J, Tanner K, Schechter CB, Scherer PE, et al. Adiponectin levels and genotype: a potential regulator of life span in humans. J Gerontol A Biol Sci Med Sci. 2008;63:447–53.PubMed

13.

Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med. 2002;8:731–7.PubMedCrossRef

14.

Ohashi K, Kihara S, Ouchi N, Kumada M, Fujita K, Hiuge A, et al. Adiponectin replenishment ameliorates obesity-related hypertension. Hypertension. 2006;47:1108–16.PubMedCrossRef

15.

Okamoto Y, Folco E, Minami M, Wara A, Feinberg M, Sukhova G, et al. Adiponectin inhibits the production of CXC receptor 3 chemokine ligands in macrophages and reduces T-lymphocyte recruitment in atherogenesis. Circ Res. 2008;102:218–25.PubMedCrossRef

16.

Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M, et al. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2002;106:2767–70.PubMedCrossRef

17.

Takemura Y, Ouchi N, Shibata R, Aprahamian T, Kirber MT, Summer RS, et al. Adiponectin modulates inflammatory reactions via calreticulin receptor-dependent clearance of early apoptotic bodies. J Clin Invest. 2007;117:375–86.PubMedCrossRef

18.

Shibata R, Ouchi N, Ito M, Kihara S, Shiojima I, Pimentel DR, et al. Adiponectin-mediated modulation of hypertrophic signals in the heart. Nat Med. 2004;10:1384–9.PubMedCrossRef

19.

Shibata R, Ouchi N, Kihara S, Sato K, Funahashi T, Walsh K. Adiponectin stimulates angiogenesis in response to tissue ischemia through stimulation of amp-activated protein kinase signaling. J Biol Chem. 2004;279:28670–4.PubMedCrossRef

20.

Shibata R, Sato K, Pimentel DR, Takemura Y, Kihara S, Ohashi K, et al. Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2-dependent mechanisms. Nat Med. 2005;11:1096–103.PubMedCrossRef

21.

Engeli S, Feldpausch M, Gorzelniak K, Hartwig F, Heintze U, Janke J, et al. Association between adiponectin and mediators of inflammation in obese women. Diabetes. 2003;52:942–7.PubMedCrossRef

22.

Esposito K, Pontillo A, Di Palo C, Giugliano G, Masella M, Marfella R, et al. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA. 2003;289:1799–804.PubMedCrossRef

23.

Krakoff J, Funahashi T, Stehouwer CD, Schalkwijk CG, Tanaka S, Matsuzawa Y, et al. Inflammatory markers, adiponectin, and risk of type 2 diabetes in the Pima Indian. Diab Care. 2003;26:1745–51.CrossRef

24.

Ouchi N, Kihara S, Funahashi T, Nakamura T, Nishida M, Kumada M, et al. Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue. Circulation. 2003;107:671–4.PubMedCrossRef

25.

Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N, et al. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood. 2000;96:1723–32.PubMed

26.

Fantuzzi G. Adiponectin and inflammation: consensus and controversy. J Allergy Clin Immunol. 2008;121:326–30.PubMedCrossRef

27.

Sada KE, Yamasaki Y, Maruyama M, Sugiyama H, Yamamura M, Maeshima Y, et al. Altered levels of adipocytokines in association with insulin resistance in patients with systemic lupus erythematosus. J Rheumatol. 2006;33:1545–52.PubMed

28.

Schaffler A, Ehling A, Neumann E, Herfarth H, Tarner I, Scholmerich J, et al. Adipocytokines in synovial fluid. JAMA. 2003;290:1709–10.PubMedCrossRef

29.

Furuta M, Tamai M, Hanabusa T, Yamamoto Y, Nanjo K, Sanke T. Serum adiponectin is associated with fasting serum C-peptide in non-obese diabetic patients. Diabetes Res Clin Pract. 2006;72:302–7.PubMedCrossRef

30.

Perseghin G, Lattuada G, Danna M, Sereni LP, Maffi P, De Cobelli F, et al. Insulin resistance, intramyocellular lipid content, and plasma adiponectin in patients with type 1 diabetes. Am J Physiol Endocrinol Metab. 2003;285:E1174–81.PubMed

31.

Bickerstaff MC, Botto M, Hutchinson WL, Herbert J, Tennent GA, Bybee A, et al. Serum amyloid P component controls chromatin degradation and prevents antinuclear autoimmunity. Nat Med. 1999;5:694–7.PubMedCrossRef

32.

Cohen PL, Eisenberg RA. Lpr and gld: single gene models of systemic autoimmunity and lymphoproliferative disease. Annu Rev Immunol. 1991;9:243–69.PubMedCrossRef

33.

Watanabe-Fukunaga R, Brannan CI, Copeland NG, Jenkins NA, Nagata S. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature. 1992;356:314–7.PubMedCrossRef

34.

Theofilopoulos AN, Dixon FJ. Murine models of systemic lupus erythematosus. Adv Immunol. 1985;37:269–390.PubMedCrossRef

35.

Aprahamian T, Bonegio RG, Richez C, Yasuda K, Chiang LK, Sato K, et al. The peroxisome proliferator-activated receptor gamma agonist rosiglitazone ameliorates murine lupus by induction of adiponectin. J Immunol. 2009;182:340–6.PubMed

36.

Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF. A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem. 1995;270:26746–9.PubMedCrossRef

37.

Suzuki S, Wilson-Kubalek EM, Wert D, Tsao TS, Lee DH. The oligomeric structure of high molecular weight adiponectin. FEBS Lett. 2007;581:809–14.PubMedCrossRef

38.

Peake PW, Shen Y, Walther A, Charlesworth JA. Adiponectin binds C1q and activates the classical pathway of complement. Biochem Biophys Res Commun. 2008;367:560–5.PubMedCrossRef

39.

Rovin BH, Song H, Hebert LA, Nadasdy T, Nadasdy G, Birmingham DJ, et al. Plasma, urine, and renal expression of adiponectin in human systemic lupus erythematosus. Kidney Int. 2005;68:1825–33.PubMedCrossRef

40.

Song H, Chan J, Rovin BH. Induction of chemokine expression by adiponectin in vitro is isoform dependent. Transl Res. 2009;154:18–26.PubMedCrossRef

41.

Vadacca M, Margiotta D, Rigon A, Cacciapaglia F, Coppolino G, Amoroso A, et al. Adipokines and systemic lupus erythematosus: relationship with metabolic syndrome and cardiovascular disease risk factors. J Rheumatol. 2009;36:295–7.PubMedCrossRef

42.

Bruce CR, Mertz VA, Heigenhauser GJ, Dyck DJ. The stimulatory effect of globular adiponectin on insulin-stimulated glucose uptake and fatty acid oxidation is impaired in skeletal muscle from obese subjects. Diabetes. 2005;54:3154–60.PubMedCrossRef

43.

Panchapakesan U, Chen XM, Pollock CA. Drug insight: thiazolidinediones and diabetic nephropathy—relevance to renoprotection. Nat Clin Pract Nephrol. 2005;1:33–43.PubMedCrossRef

44.

Mullen KL, Smith AC, Junkin KA, Dyck DJ. Globular adiponectin resistance develops independently of impaired insulin-stimulated glucose transport in soleus muscle from high-fat fed rats. Am J Physiol Endocrinol Metab. 2007;293:E83–90.PubMedCrossRef

45.

Zandman-Goddard G, Peeva E, Shoenfeld Y. Gender and autoimmunity. Autoimmun Rev. 2007;6:366–72.PubMedCrossRef

Titel: Modulation of Lupus Phenotype by Adiponectin Deficiency in Autoimmune Mouse Models
verfasst von: Jennifer Parker
Hanni Menn-Josephy
Bari Laskow
Yukihiro Takemura
Tamar Aprahamian
Publikationsdatum: 01.04.2011
Verlag: Springer US
Erschienen in: Journal of Clinical Immunology / Ausgabe 2/2011
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-010-9486-2

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

„Jeder Fall von plötzlichem Tod muss obduziert werden!“

17.05.2024 Plötzlicher Herztod Nachrichten

Ein signifikanter Anteil der Fälle von plötzlichem Herztod ist genetisch bedingt. Um ihre Verwandten vor diesem Schicksal zu bewahren, sollten jüngere Personen, die plötzlich unerwartet versterben, ausnahmslos einer Autopsie unterzogen werden.

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Schlechtere Vorhofflimmern-Prognose bei kleinem linken Ventrikel

17.05.2024 Vorhofflimmern Nachrichten

Nicht nur ein vergrößerter, sondern auch ein kleiner linker Ventrikel ist bei Vorhofflimmern mit einer erhöhten Komplikationsrate assoziiert. Der Zusammenhang besteht nach Daten aus China unabhängig von anderen Risikofaktoren.

Semaglutid bei Herzinsuffizienz: Wie erklärt sich die Wirksamkeit?

17.05.2024 Herzinsuffizienz Nachrichten

Bei adipösen Patienten mit Herzinsuffizienz des HFpEF-Phänotyps ist Semaglutid von symptomatischem Nutzen. Resultiert dieser Benefit allein aus der Gewichtsreduktion oder auch aus spezifischen Effekten auf die Herzinsuffizienz-Pathogenese? Eine neue Analyse gibt Aufschluss.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2011

FOXP3, IL-10, and TGF-β Genes Expression in Children with IgE-Dependent Food Allergy

Oxytetracycline Attenuates Allergic Airway Inflammation in Mice via Inhibition of the NF-κB Pathway

Hepatitis B e-antigen Persistency is Associated with the Properties of HBV-Specific CD8 T Cells in CHB Patients

ICF Syndrome in Saudi Arabia: Immunological, Cytogenetic and Molecular Analysis

Lactobacillus casei reduces the Inflammatory Joint Damage Associated with Collagen-Induced Arthritis (CIA) by Reducing the Pro-Inflammatory Cytokines