Top

Journal of Clinical Immunology

Published in:

01-09-2009

Differential Transcriptional Expression of PPARα, PPARγ1, and PPARγ2 in the Peritoneal Macrophages and T-cell Subsets of Non-obese Diabetic Mice

Authors: Nik-Soriani Yaacob, Mohd Arifin Kaderi, Mohd-Nor Norazmi

Published in: Journal of Clinical Immunology | Issue 5/2009

Abstract

Background

The peroxisome proliferator-activated receptors (PPARs) have been implicated in immune regulation. We determined the transcriptional expression of the three isoforms, PPARα, PPARγ1, and PPARγ2 in the peritoneal macrophages, CD4- and CD8-positive lymphocytes in non-obese diabetic (NOD) mice at 5 and 10 weeks of age as well as at diabetic stage.

Results

Compared to the non-obese diabetic resistant (NOR) mice, the peritoneal macrophages of NOD mice expressed increased levels of PPARα but reduced levels of PPARγ2, while PPARγ1 expression was unchanged in all age groups. CD4-positive lymphocytes expressed low levels of PPARα in diabetic NOD mice and greatly reduced expression of PPARγ2 in all age groups. Unlike peritoneal macrophages and CD4-positive cells, the CD8-positive cells expressed low levels of PPARγ1 in diabetic NOD mice but no difference in PPARα and PPARγ2 expression was observed compared to NOR mice.

Conclusion

The current findings may suggest an important regulatory role of PPARs in the pathogenesis of autoimmune diabetes.

Hutchings P, Rosen H, O’Reilly L, Simpson E, Gordon S, Cooke A. Transfer of diabetes in mice prevented by blockage of adhesion-promoting receptors on macrophages. Nature. 1990;348:639–42. doi:10.1038/348639a0.PubMedCrossRef

Bendelac A, Carnaud C, Boitard C, Bach JF. Syngeneic transfer of autoimmune diabetes from diabetic NOD mice to healthy neonates. Requirement for both L3T4+ and Lyt-2+ T cells. J Exp Med. 1987;166:823–32. doi:10.1084/jem.166.4.823.PubMedCrossRef

Yaacob NS, Kaderi MA, Norazmi MN. The expression of cytokine genes in the peritoneal macrophages and splenic CD4- and CD8-positive lymphocytes of the non-obese diabetic mice. J Clin Immunol. 2004;24:177–84. doi:10.1023/B:JOCI.0000019783.61674.1d.PubMedCrossRef

Rabinovitch A. Immunoregulatory and cytokine imbalances in the pathogenesis of IDDM. Therapeutic intervention by immunostimulation? Diabetes. 1994;43:613–21. doi:10.2337/diabetes.43.5.613.PubMedCrossRef

Isseman I, Green S. Activation of a number of the steroid receptor superfamily by peroxisome proliferators. Nature. 1990;347:645–50. doi:10.1038/347645a0.CrossRef

Kliewer SA, Forman BM, Blumberg B, Ong ES, Borgmeyer U, Mangelsdorf DJ, et al. Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proc Natl Acad Sci U S A. 1994;91:7355–9. doi:10.1073/pnas.91.15.7355.PubMedCrossRef

Braissant O, Foufelle F, Scotto C, Dauca M, Wahli W. Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta and -gamma in the adult rat. Endocrinology. 1996;137:354–66. doi:10.1210/en.137.1.354.PubMedCrossRef

Vidal-Puig AJ, Considine RV, Jimenez-Linan M, Werman A, Pories WJ, Caro JF, et al. Peroxisome proliferator-activated receptor gene expression in human tissues. Effects of obesity, weight loss, and regulation by insulin and glucocorticoids. J Clin Invest. 1997;99:2416–22. doi:10.1172/JCI119424.PubMedCrossRef

Lampen A, Carlberg C, Nau H. Peroxisome proliferator-activated receptor delta is a specific sensor for teratogenic valproic acid derivatives. Eur J Pharmacol. 2001;431:25–33. doi:10.1016/S0014-2999(01)01423-6.PubMedCrossRef

10.

Tontonoz P, Hu E, Spiegelman BM. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell. 1994;79:1147–56. doi:10.1016/0092-8674(94)90006-X.PubMedCrossRef

11.

Zhu Y, Qi C, Korenberg JR, Chen XN, Noya D, Rao MS, et al. Structural organization of mouse peroxisome proliferator-activated receptor gamma (mPPAR gamma) gene: alternative promoter use and different splicing yield two mPPAR gamma isoforms. Proc Natl Acad Sci U S A. 1995;92:7921–5. doi:10.1073/pnas.92.17.7921.PubMedCrossRef

12.

Michalik L, Auwerx J, Berger JP, Chatterjee VK, Glass CK, Gonzalez FJ, et al. International Union of Pharmacology LXI. Peroxisome proliferator-activated receptors. Pharmacol Rev. 2006;58:726–41. doi:10.1124/pr.58.4.5.PubMedCrossRef

13.

Daynes RA, Jones DC. Emerging roles of PPARs in inflammation and immunity. Nat Rev Immunol. 2002;2:748–59. doi:10.1038/nri912.PubMedCrossRef

14.

Jiang C, Ting AT, Seed B. PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature. 1998;391:82–6. doi:10.1038/35154.PubMedCrossRef

15.

Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK. The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature. 1998;391:79–82. doi:10.1038/34178.PubMedCrossRef

16.

Yang XY, Wang LH, Chen T, Hodge DR, Resau JH, DaSilva L, et al. Activation of human T lymphocytes is inhibited by peroxisome proliferator-activated receptor gamma (PPARgamma) agonists. PPARgamma co-association with transcription factor NFAT. J Biol Chem. 2000;275:4541–4. doi:10.1074/jbc.275.7.4541.PubMedCrossRef

17.

Augstein P, Dunger A, Heinke P, Wachlin G, Berg S, Hehmke B, et al. Prevention of autoimmune diabetes in NOD mice by troglitazone is associated with modulation of ICAM-1 expression on pancreatic islet cells and IFNg expression in splenic T cells. Biochem Biophys Res Commun. 2003;304:378–84. doi:10.1016/S0006-291X(03)00590-4.PubMedCrossRef

18.

Awara WM, El-Sisi AE, El-Refaei M, El-Naa MM, El-Desoky K. Insulinotropic and anti-inflammatory effects of rosiglitazone in experimental autoimmune diabetes. Rev Diabet Stud. 2005;2:146–56. doi:10.1900/RDS.2005.2.146.PubMedCrossRef

19.

Reddy S, Liu W, Elliott RB. Distribution of pancreatic macrophages preceding and during early insulitis in young NOD mice. Pancreas. 1993;8:602–8. doi:10.1097/00006676-199309000-00012.PubMedCrossRef

20.

Pozzilli P, Signore A, Williams AJ, Beales PE. NOD mouse colonies around the world—recent facts and figures. Immunol Today. 1993;14:193–6. doi:10.1016/0167-5699(93)90160-M.PubMedCrossRef

21.

Clark RB, Bishop-Bailey D, Estrada-Hernandez T, Hla T, Puddington L, Padula SJ. The nuclear receptor PPAR gamma and immunoregulation: PPAR gamma mediates inhibition of helper T cell responses. J Immunol. 2000;164:1364–71.PubMed

22.

Yoon JW, Jun HS, Santamaria P. Cellular and molecular mechanisms for the initiation and progression of beta cell destruction resulting from the collaboration between macrophages and T cells. Autoimmunity. 1998;27:109–22. doi:10.3109/08916939809008041.PubMedCrossRef

23.

McDuffie M, Maybee NA, Keller SR, Stevens BK, Garmey JC, Morris MA, et al. Nonobese diabetic (NOD) mice congenic for a targeted deletion of 12/15-lipoxygenase are protective from autoimmune diabetes. Diabetes. 2008;57:199–208. doi:10.2337/db07-0830.PubMedCrossRef

24.

Middleton MK, Rubinstein T, Pure E. Cellular and molecular mechanisms of the selective regulation of IL-12 production by 12/15-lipoxygenase. J Immunol. 2006;176:265–74.PubMed

25.

Yu Z, Scheider C, Boeglin WE, Brash AR. Epidermal lipoxygenase products of the hepoxilin pathway selectively activate the nuclear receptor PPARα. Lipids. 2007;42:491–7. doi:10.1007/s11745-007-3054-4.PubMedCrossRef

26.

Tontonoz P, Nagy L, Alvarez JGA, Thomazy VA, Evans RM. PPARγ promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell. 1998;93:241–52. doi:10.1016/S0092-8674(00)81575-5.PubMedCrossRef

27.

Li M, Pascual G, Glass CK. Peroxisome proliferator-activated receptor gamma-dependent repression of the inducible nitric oxide synthase gene. Mol Cell Biol. 2000;20:4699–707. doi:10.1128/MCB.20.13.4699-4707.2000.PubMedCrossRef

28.

Cunard R, Ricote M, DiCampli D, Archer DC, Kahn DA, Glass CK, et al. Regulation of cytokine expression by ligands of peroxisome proliferator activated receptors. J Immunol. 2002;168:2795–802.PubMed

29.

Jones DC, Ding X, Daynes RA. Nuclear receptor peroxisome proliferator-activated receptor α (PPARα) is expressed in resting murine lymphocytes. The PPARα in T and B lymphocytes is both transactivation and transrepressioncompetent. J Biol Chem. 2002;277:6838–45. doi:10.1074/jbc.M106908200.PubMedCrossRef

30.

Dreyer C, Krey G, Keller H, Givel F, Helftenbein G, Wahli W. Control of the peroxisomal beta-oxidation pathway by a novel family of nuclear hormone receptors. Cell. 1992;68:879–87. doi:10.1016/0092-8674(92)90031-7.PubMedCrossRef

31.

Marx N, Kehrle B, Kohlhammer K, Grüb M, Koenig W, Hombach V, et al. PPAR activators as antiinflammatory mediators in human T lymphocytes: implications for atherosclerosis and transplantation-associated arteriosclerosis. Circ Res. 2002;90:703–10. doi:10.1161/01.RES.0000014225.20727.8F.PubMedCrossRef

32.

Wang P, Anderson PO, Chen S, Paulsson KM, Sjogren HO, Li S. Inhibition of the transcription factors AP-1 and NF-kappaB in CD4 T cells by peroxisome proliferator-activated receptor gamma ligands. Int Immunopharmacol. 2001;1:803–12. doi:10.1016/S1567-5769(01)00015-7.PubMedCrossRef

33.

Saubermann LJ, Nakajima A, Wada K, Zhao S, Terauchi Y, Kadowaki T, et al. Peroxisome proliferator-activated receptor gamma agonist ligands stimulate Th2 cytokine response and prevent acute colitis. Inflamm Bowel Dis. 2002;8:330–9. doi:10.1097/00054725-200209000-00004.PubMedCrossRef

34.

Yoshida K, Kikutani H. Genetic and immunological basis of autoimmune diabetes in the NOD mouse. Rev Immunogenet. 2000;2:140–6.PubMed

Title: Differential Transcriptional Expression of PPARα, PPARγ1, and PPARγ2 in the Peritoneal Macrophages and T-cell Subsets of Non-obese Diabetic Mice
Authors: Nik-Soriani Yaacob
Mohd Arifin Kaderi
Mohd-Nor Norazmi
Publication date: 01-09-2009
Publisher: Springer US
Published in: Journal of Clinical Immunology / Issue 5/2009
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-009-9300-1

ACC 2024 Congress Coverage

Heart Failure Video

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Differential Transcriptional Expression of PPARα, PPARγ1, and PPARγ2 in the Peritoneal Macrophages and T-cell Subsets of Non-obese Diabetic Mice

Abstract

Background

Results

Conclusion

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

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

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 5/2009

Chronic Arsenic Exposure Impairs Macrophage Functions in the Exposed Individuals

Sequential Changes in Serum Cytokines Reflect Viral RNA Kinetics in Target Organs of a Coxsackievirus B Infection in Mice

Major Hepatectomy Induces Phenotypic Changes in Circulating Dendritic Cells and Monocytes

Interleukin 18 Promoter Variants (−137G>C and −607C>A) in Patients with Chronic Hepatitis C: Association with Treatment Response

A Novel Mutation in a Patient with a Deficiency of the Eighth Component of Complement Associated with Recurrent Meningococcal Meningitis

siRNA Knockdown of PD-L1 and PD-L2 in Monocyte-Derived Dendritic Cells only Modestly Improves Proliferative Responses to Gag by CD8+ T Cells from HIV-1-Infected Individuals

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

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

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page