Emerging roles of PPARS in inflammation and immunity (original) (raw)

• Desvergne, B. & Wahli, W. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev 20, 649–688 (1999).
  CAS PubMed Google Scholar
• Clark, RB. The role of PPARs in inflammation and immunity. J Leukoc Biol 71, 388–400 (2002).
  CAS PubMed Google Scholar
• Chinetti, G. et al. Activation of proliferator-activated receptors α and γ induces apoptosis of human monocyte-derived macrophages. J. Biol. Chem. 273, 25573–25580 (1998).
  Article CAS PubMed Google Scholar
• 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 transrepression competent. J Biol Chem 277, 6838–6845 (2002).This paper, together with reference 83 , was the first to describe the presence of PPARα in lymphocytes and to establish a role for this nuclear receptor in the regulation of cytokine production by activated T cells.
  Article CAS PubMed Google Scholar
• Gosset, P. et al. Peroxisome proliferator-activated receptor γ activators affect the maturation of human monocyte-derived dendritic cells. Eur J Immunol. 31, 2857–2865 (2001).This paper describes a role for PPARγ in the regulation of dendritic-cell maturation, and cytokine and chemokine production.
  Article CAS PubMed Google Scholar
• Harris, S. G. & Phipps, R. P. The nuclear receptor PPARγ is expressed by mouse T lymphocytes and PPARγ agonists induce apoptosis. Eur. J. Immunol. 31, 1098–1105 (2001).
  Article CAS PubMed Google Scholar
• Alleva, D. G. et al. Regulation of murine macrophage proinflammatory and anti-inflammatory cytokines by ligands for peroxisome proliferator-activated receptor-γ: counter-regulatory activity by IFN-γ. J. Leukocyte Biol. 71, 677–685 (2002).
  CAS PubMed Google Scholar
• Setoguchi, K. et al. Peroxisome proliferator-activated receptor-γ haploinsufficiency enhances B-cell proliferative responses and exacerbates experimentally induced arthritis. J. Clin. Invest. 108, 1667–1675 (2001).This study used Pparγ +/− mice to describe a role for PPARγ in B-cell physiology. It showed that these mice have increased levels of circulating IgG and IgM and are more susceptible to autoimmune diseases.
  Article CAS PubMed PubMed Central Google Scholar
• Rotondo, D. & Davidson, J. Prostaglandin and PPAR control of immune-cell function. Immunology 105, 20–22 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Padilla, J., Kaur, K., Cao, H. J., Smith, T. J. & Phipps, R. P. Peroxisome proliferator activator receptor-γ agonists and 15-deoxy-Δ12,14-PGJ2 induce apoptosis in normal and malignant B-lineage cells. J. Immunol. 165, 6941–6948 (2000).This was the first report to describe the presence of PPARγ in B cells.
  Article CAS PubMed Google Scholar
• Issemann, I. & Green, S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 347, 645–650 (1990).
  Article CAS PubMed Google Scholar
• Corton, J. C., Anderson, S. P. & Stauber, A. Central role of peroxisome proliferator-activated receptors in the actions of peroxisome proliferators. Ann. Rev. Pharmacol. Toxicol. 40, 491–518 (2000).
  Article CAS Google Scholar
• Gonzalez, F. J. The role of peroxisome proliferator-activated receptor-α in peroxisome proliferation, physiological homeostasis and chemical carcinogenesis. Adv. Exp. Med. Biol. 422, 109–125 (1997).
  Article CAS PubMed Google Scholar
• Dreyer, C. et al. Control of the peroxisomal β-oxidation pathway by a novel family of nuclear hormone receptors. Cell 68, 879–887 (1992).
  Article CAS PubMed Google Scholar
• Laudet, V., Hanni, C., Coll, J., Catzeflis, F. & Stehelin, D. Evolution of the nuclear receptor gene superfamily. EMBO J. 11, 1003–1013 (1992).
  Article CAS PubMed PubMed Central Google Scholar
• Miyata, K. S., McCaw, S. E., Marcus, S. L., Rachubinski, R. A. & Capone, J. P. The peroxisome proliferator-activated receptor interacts with the retinoid X receptor in vivo. Gene 148, 327–330 (1994).
  Article CAS PubMed Google Scholar
• Tugwood, J. D. et al. The mouse peroxisome proliferator-activated receptor recognizes a response element in the 5′ flanking sequence of the rat acyl CoA oxidase gene. EMBO J. 11, 433–439 (1992).
  Article CAS PubMed PubMed Central Google Scholar
• Mascaro, C. et al. Characterization of a response element for peroxisomal proliferator-activated receptor (PPRE) in human muscle-type carnitine palmitoyltransferase I. Adv. Exp. Med. Biol. 466, 79–85 (1999).
  Article CAS PubMed Google Scholar
• Green, S. & Wahli, W. Peroxisome proliferator-activated receptors: finding the orphan a home. Mol. Cell. Endocrinol. 100, 149–153 (1994).
  Article CAS PubMed Google Scholar
• IJpenberg, A., Jeannin, E., Wahli, W. & Desvergne, B. Polarity and specific sequence requirements of peroxisome proliferator-activated receptor (PPAR)/retinoid X receptor heterodimer binding to DNA. A functional analysis of the malic enzyme gene PPAR response element. J. Biol. Chem. 272, 20108–20117 (1997).
  Article CAS PubMed Google Scholar
• Gervois, P. et al. Fibrates increase human REV-ERBα expression in liver via a novel peroxisome proliferator-activated receptor response element. Mol. Endocrinol. 13, 400–409 (1999).
  CAS PubMed Google Scholar
• Zhu, Y., Qi, C., Calandra, C., Rao, M. S. & Reddy, J. K. Cloning and identification of mouse steroid receptor coactivator-1 (mSRC-1), as a coactivator of peroxisome proliferator-activated receptor-γ. Gene Expr. 6, 185–195 (1996).
  CAS PubMed Google Scholar
• Zamir, I., Zhang, J. & Lazar, M. A. Stoichiometric and steric principles governing repression by nuclear hormone receptors. Genes Dev. 11, 835–846 (1997).
  Article CAS PubMed Google Scholar
• Hassig, C. A., Fleischer, T. C., Billin, A. N., Schreiber, S. L. & Ayer, D. E. Histone deacetylase activity is required for full transcriptional repression by mSin3A. Cell 89, 341–347 (1997).
  Article CAS PubMed Google Scholar
• Dowell, P. et al. Identification of nuclear receptor corepressor as a peroxisome proliferator-activated receptor-α-interacting protein. J. Biol. Chem. 274, 15901–15907 (1999).
  Article CAS PubMed Google Scholar
• Shi, Y., Hon, M. & Evans, R. M. The peroxisome proliferator-activated receptor-δ, an integrator of transcriptional repression and nuclear-receptor signaling. Proc. Natl Acad. Sci. USA 99, 2613–2618 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• DiRenzo, J. et al. Peroxisome proliferator-activated receptors and retinoic-acid receptors differentially control the interactions of retinoid X receptor heterodimers with ligands, coactivators and corepressors. Mol. Cell. Biol. 17, 2166–2176 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Dowell, P. et al. p300 functions as a coactivator for the peroxisome proliferator-activated receptor-α. J. Biol. Chem. 272, 33435–33443 (1997).
  Article CAS PubMed Google Scholar
• Zhu, Y., Qi, C., Jain, S., Rao, M. S. & Reddy, J. K. Isolation and characterization of PBP, a protein that interacts with peroxisome proliferator-activated receptor. J. Biol. Chem. 272, 25500–25506 (1997).
  Article CAS PubMed Google Scholar
• Yuan, C. X., Ito, M., Fondell, J. D., Fu, Z. Y. & Roeder, R. G. The TRAP220 component of a thyroid hormone receptor-associated protein (TRAP) coactivator complex interacts directly with nuclear receptors in a ligand-dependent fashion. Proc. Natl Acad. Sci. USA 95, 7939–7944 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Xu, H. E. et al. Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol. Cell 3, 397–403 (1999).
  Article CAS PubMed Google Scholar
• Gottlicher, M., Widmark, E., Li, Q. & Gustafsson, J. A. Fatty acids activate a chimera of the clofibric-acid-activated receptor and the glucocorticoid receptor. Proc. Natl Acad. Sci. USA 89, 4653–4657 (1992).
  Article CAS PubMed PubMed Central Google Scholar
• Kliewer, S. A. et al. A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor-γ and promotes adipocyte differentiation. Cell 83, 813–819 (1995).
  Article CAS PubMed Google Scholar
• Shibata, T. et al. 15-deoxy-Δ12,14-prostaglandin J2. A prostaglandin D2 metabolite generated during inflammatory processes. J. Biol. Chem. 277, 10459–10466 (2002).
  Article CAS PubMed Google Scholar
• Forman, B. M., Chen, J. & Evans, R. M. Hypolipidemic drugs, polyunsaturated fatty acids and eicosanoids are ligands for peroxisome proliferator-activated receptors α and δ. Proc. Natl Acad. Sci. USA 94, 4312–4317 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Laffitte, B. A. et al. Autoregulation of the human liver X receptor α promoter. Mol. Cell. Biol. 21, 7558–7568 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Leibowitz, M. D. et al. Activation of PPARδ alters lipid metabolism in db/db mice. Fed. Eur. Biochem. Soc. Letts 473, 333–336 (2000).
  Article CAS Google Scholar
• Oliver, W. R. Jr et al. A selective peroxisome proliferator-activated receptor δ agonist promotes reverse cholesterol transport. Proc. Natl Acad. Sci. USA 98, 5306–5311 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Vosper, H. et al. The peroxisome proliferator-activated receptor δ promotes lipid accumulation in human macrophages. J. Biol. Chem. 276, 44258–44265 (2001).
  Article CAS PubMed Google Scholar
• Delerive, P., Fruchart, J. C. & Staels, B. Peroxisome proliferator-activated receptors in inflammation control. J. Endocrinol. 169, 453–459 (2001).
  Article CAS PubMed Google Scholar
• Poynter, M. E. & Daynes, R. A. Peroxisome proliferator-activated receptor-α activation modulates cellular redox status, represses nuclear factor-κB signaling and reduces inflammatory cytokine production in aging. J. Biol. Chem. 273, 32833–32841 (1998).
  Article CAS PubMed Google Scholar
• Ricote, M., Li, A. C., Willson, T. M., Kelly, C. J. & Glass, C. K. The peroxisome proliferator-activated receptor-γ is a negative regulator of macrophage activation. Nature 391, 79–82 (1998).
  Article CAS PubMed Google Scholar
• Li, M., Pascual, G. & Glass, C. K. Peroxisome proliferator-activated receptor-γ-dependent repression of the inducible nitric oxide synthase gene. Mol. Cell. Biol. 20, 4699–4707 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Delerive, P. et al. Peroxisome proliferator-activated receptor-α negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factors NF-κB and AP-1. J. Biol. Chem. 274, 32048–32054 (1999).
  Article CAS PubMed Google Scholar
• Delerive, P. et al. Peroxisome proliferator-activated receptor activators inhibit thrombin-induced endothelin-1 production in human vascular endothelial cells by inhibiting the activator protein-1 signaling pathway. Circulation Res. 85, 394–402 (1999).
  Article CAS PubMed Google Scholar
• Delerive, P., Gervois, P., Fruchart, J. C. & Staels, B. Induction of IκBα expression as a mechanism contributing to the anti-inflammatory activities of peroxisome proliferator-activated receptor-α activators. J. Biol. Chem. 275, 36703–36707 (2000).
  Article CAS PubMed Google Scholar
• Desreumaux, P. et al. Attenuation of colon inflammation through activators of the retinoid X receptor (RXR)/peroxisome proliferator-activated receptor-γ (PPARγ) heterodimer. A basis for new therapeutic strategies. J. Exp. Med. 193, 827–838 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Tan, N. S. et al. Critical roles of PPARβ/δ in keratinocyte response to inflammation. Genes Dev. 15, 3263–3277 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Devchand, P. R. et al. The PPARα–leukotriene-B4 pathway to inflammation control. Nature 384, 39–43 (1996).A key paper that used Pparα −/− mice to describe a role for PPARα in the regulation of inflammation.
  Article CAS PubMed Google Scholar
• Field, C. J., Johnson, I. R. & Schley, P. D. Nutrients and their role in host resistance to infection. J. Leukocyte Biol. 71, 16–32 (2002).
  CAS PubMed Google Scholar
• Grimble, R. F. Nutritional modulation of immune function. Proc. Nutr. Soc. 60, 389–397 (2001).
  Article CAS PubMed Google Scholar
• Spencer, N. F., Poynter, M. E., Hennebold, J. D., Mu, H. H. & Daynes, R. A. Does DHEAS restore immune competence in aged animals through its capacity to function as a natural modulator of peroxisome activities? Ann. NY Acad. Sci. 774, 200–216 (1995).
  Article CAS PubMed Google Scholar
• Weksler, M. E. Immune senescence and adrenal steroids: immune dysregulation and the action of dehydroepiandrosterone (DHEA) in old animals. Eur. J. Clin. Pharmacol. 45, S21–S23 (1993).
  Article CAS PubMed Google Scholar
• Jump, D. B. & Clarke, S. D. Regulation of gene expression by dietary fat. Ann. Rev. Nutr. 19, 63–90 (1999).
  Article CAS Google Scholar
• Peters, J. M. et al. Peroxisome proliferator-activated receptor-α required for gene induction by dehydroepiandrosterone-3 β-sulfate. Mol. Pharmacol. 50, 67–74 (1996).
  CAS PubMed Google Scholar
• Staels, B. et al. Activation of human aortic smooth-muscle cells is inhibited by PPARα but not by PPARγ activators. Nature 393, 790–793 (1998).
  Article CAS PubMed Google Scholar
• Jiang, C., Ting, A. T. & Seed, B. PPAR-γ agonists inhibit production of monocyte inflammatory cytokines. Nature 391, 82–86 (1998).
  Article CAS PubMed Google Scholar
• Kippenberger, S. et al. Activators of peroxisome proliferator-activated receptors protect human skin from ultraviolet-B-light-induced inflammation. J. Invest. Dermatol. 117, 1430–1436 (2001).
  Article CAS PubMed Google Scholar
• Combs, C. K., Bates, P., Karlo, J. C. & Landreth, G. E. Regulation of β-amyloid-stimulated proinflammatory responses by peroxisome proliferator-activated receptor-α. Neurochem. Int. 39, 449–457 (2001).
  Article CAS PubMed Google Scholar
• Gupta, R. A. et al. Activation of peroxisome proliferator-activated receptor γ suppresses nuclear factor-κB-mediated apoptosis induced by Helicobacter pylori in gastric epithelial cells. J. Biol. Chem. 276, 31059–31066 (2001).
  Article CAS PubMed Google Scholar
• Willson, T. M., Brown, P. J., Sternbach, D. D. & Henke, B. R. The PPARs: from orphan receptors to drug discovery. J. Med. Chem. 43, 527–550 (2000).
  Article CAS PubMed Google Scholar
• Chawla, A. et al. PPAR-γ-dependent and -independent effects on macrophage-gene expression in lipid metabolism and inflammation. Nature Med. 7, 48–52 (2001).This paper used macrophages derived from Pparγ −/− embryonic stem cells to describe PPARγ-independent and -dependant effects on the regulation of gene transcription.
  Article CAS PubMed Google Scholar
• Castrillo, A., Diaz-Guerra, M. J., Hortelano, S., Martin-Sanz, P. & Bosca, L. Inhibition of IκB kinase and IκB phosphorylation by 15-deoxy-Δ12,14-prostaglandin J2 in activated murine macrophages. Mol. Cell. Biol. 20, 1692–1698 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Straus, D. S. et al. 15-deoxy-Δ12,14-prostaglandin J2 inhibits multiple steps in the NF-κB signaling pathway. Proc. Natl Acad. Sci. USA 97, 4844–4849 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Rival, Y. et al. PPARα and PPARδ activators inhibit cytokine-induced nuclear translocation of NF-κB and expression of VCAM-1 in EAhy926 endothelial cells. Eur. J. Pharmacol. 435, 143–151 (2002).
  Article CAS PubMed Google Scholar
• Michalik, L. et al. Impaired skin-wound healing in peroxisome proliferator-activated receptor (PPAR)α and PPARβ mutant mice. J. Cell Biol. 154, 799–814 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Peters, J. M. et al. Growth, adipose, brain and skin alterations resulting from targeted disruption of the mouse peroxisome proliferator-activated receptor β(δ). Mol. Cell. Biol. 20, 5119–5128 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Li, M. et al. An essential role of the NF-κB/Toll-like receptor pathway in induction of inflammatory and tissue-repair gene expression by necrotic cells. J. Immunol. 166, 7128–7135 (2001).
  Article CAS PubMed Google Scholar
• Komuves, L. G. et al. Keratinocyte differentiation in hyperproliferative epidermis: topical application of PPARα activators restores tissue homeostasis. J. Invest. Dermatol. 115, 361–367 (2000).
  Article CAS PubMed Google Scholar
• Tsutsumi-Ishii, Y. & Nagaoka, I. NF-κB-mediated transcriptional regulation of human β-defensin-2 gene following lipopolysaccharide stimulation. J. Leukocyte Biol. 71, 154–162 (2002).
  CAS PubMed Google Scholar
• Wada, A. et al. _Helicobacter pylori_-mediated transcriptional regulation of the human β-defensin-2 gene requires NF-κB. Cell. Microbiol. 3, 115–123 (2001).
  Article CAS PubMed Google Scholar
• Serghides, L. & Kain, K. C. Peroxisome proliferator-activated receptor-γ-retinoid X receptor agonists increase CD36-dependent phagocytosis of _Plasmodium falciparum_-parasitized erythrocytes and decrease malaria-induced TNF-α secretion by monocytes/macrophages. J. Immunol. 166, 6742–6748 (2001).
  Article CAS PubMed Google Scholar
• Hermanowski-Vosatka, A. et al. PPARα agonists reduce 11β-hydroxysteroid dehydrogenase type 1 in the liver. Biochem. Biophys. Res. Commun. 279, 330–336 (2000).
  Article CAS PubMed Google Scholar
• Berger, J. et al. Peroxisome proliferator-activated receptor-γ ligands inhibit adipocyte 11β-hydroxysteroid dehydrogenase type 1 expression and activity. J. Biol. Chem. 276, 12629–12635 (2001).
  Article CAS PubMed Google Scholar
• Yau, J. L. et al. Lack of tissue glucocorticoid reactivation in 11β-hydroxysteroid dehydrogenase type 1 knockout mice ameliorates age-related learning impairments. Proc. Natl Acad. Sci. USA 98, 4716–4721 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Morton, N. M. et al. Improved lipid and lipoprotein profile, hepatic insulin sensitivity and glucose tolerance in 11β-hydroxysteroid dehydrogenase type 1 null mice. J. Biol. Chem. 276, 41293–41300 (2001).
  Article CAS PubMed Google Scholar
• Sandeep, T. C. & Walker, B. R. Pathophysiology of modulation of local glucocorticoid levels by 11β-hydroxysteroid dehydrogenases. Trends Endocrinol. Metab. 12, 446–453 (2001).
  Article CAS PubMed Google Scholar
• Steinman, R. M., Pack, M. & Inaba, K. Dendritic-cell development and maturation. Adv. Exp. Med. Biol. 417, 1–6 (1997).
  Article CAS PubMed Google Scholar
• Mellman, I., Turley, S. J. & Steinman, R. M. Antigen processing for amateurs and professionals. Trends Cell Biol. 8, 231–237 (1998).
  Article CAS PubMed Google Scholar
• Faveeuw, C. et al. Peroxisome proliferator-activated receptor-γ activators inhibit interleukin-12 production in murine dendritic cells. Fed. Eur. Biochem. Soc. Letts 486, 261–266 (2000).
  Article CAS Google Scholar
• Yang, X. Y. et al. Activation of human T lymphocytes is inhibited by peroxisome proliferator-activated receptor-γ (PPARγ) agonists. PPARγ co-association with transcription factor NFAT. J. Biol. Chem. 275, 4541–4544 (2000).This paper was one of the first to show that the activation of PPARγ regulates T-cell cytokine production through the repression of NFAT.
  Article CAS PubMed Google Scholar
• Wang, P. et al. Inhibition of the transcription factors AP-1 and NF-κB in CD4 T cells by peroxisome proliferator-activated receptor-γ ligands. Int. Immunopharmacol. 1, 803–812 (2001).
  Article CAS PubMed Google Scholar
• Cunard, R. et al. Regulation of cytokine expression by ligands of peroxisome proliferator-activated receptors. J. Immunol. 168, 2795–2802 (2002).
  Article CAS PubMed Google Scholar
• Clark, R. B. et al. The nuclear receptor PPARγ and immunoregulation: PPARγ mediates inhibition of helper T-cell responses. J. Immunol. 164, 1364–1371 (2000).This paper was the first to show that activation of PPARγ regulates T-cell cytokine production.
  Article CAS PubMed Google Scholar
• Harris, S. G., Smith, R. S. & Phipps, R. P. 15-deoxy-Δ12,14-PGJ2 induces IL-8 production in human T cells by a mitogen-activated protein kinase pathway. J. Immunol. 168, 1372–1379 (2002).
  Article CAS PubMed Google Scholar
• Padilla, J., Leung, E. & Phipps, R. P. Human B lymphocytes and B lymphomas express PPAR-γ and are killed by PPAR-γ agonists. Clin. Immunol. 103, 22–33 (2002).
  Article CAS PubMed Google Scholar
• Yang, X. Y. et al. Interleukin (IL)-4 indirectly suppresses IL-2 production by human T lymphocytes via peroxisome proliferator-activated receptor-γ activated by macrophage-derived 12/15-lipoxygenase ligands. J. Biol. Chem. 277, 3973–3978 (2002).
  Article CAS PubMed Google Scholar
• Huang, J. T. et al. Interleukin-4-dependent production of PPARγ ligands in macrophages by 12/15-lipoxygenase. Nature 400, 378–382 (1999).
  Article CAS PubMed Google Scholar
• Chtanova, T., Kemp, R. A., Sutherland, A. P., Ronchese, F. & Mackay, C. R. Gene microarrays reveal extensive differential gene expression in both CD4+ and CD8+ type-1 and type-2 T cells. J. Immunol. 167, 3057–3063 (2001).
  Article CAS PubMed Google Scholar
• Szabo, S. J. et al. A novel transcription factor, T-bet, directs TH1 lineage commitment. Cell 100, 655–669 (2000).
  Article CAS PubMed Google Scholar
• van Vollenhoven, R. F. Dehydroepiandrosterone in systemic lupus erythematosus. Rheum. Dis. Clin. North Am. 26, 349–362 (2000).
  Article CAS PubMed Google Scholar
• Lucas, J. A., Ahmed, S. A., Casey, M. L. & MacDonald, P. C. Prevention of autoantibody formation and prolonged survival in New Zealand black/New Zealand white F1 mice fed dehydroisoandrosterone. J. Clin. Invest. 75, 2091–2093 (1985).
  Article CAS PubMed PubMed Central Google Scholar
• Karmali, R. A., Hanrahan, R., Volkman, A. & Smith, N. Prostaglandins and essential fatty acids in regulation of autoimmunity and development of antibodies to DNA in NZB x NZW F1 mice. Prog Lipid Res. 20, 655–661 (1981).
  Article CAS PubMed Google Scholar
• Ben-Nathan, D., Padgett, D. A. & Loria, R. M. Androstenediol and dehydroepiandrosterone protect mice against lethal bacterial infections and lipopolysaccharide toxicity. J. Med. Microbiol. 48, 425–431 (1999).
  Article CAS PubMed Google Scholar
• Rasmussen, K. R., Healey, M. C., Cheng, L. & Yang, S. Effects of dehydroepiandrosterone in immunosuppressed adult mice infected with Cryptosporidium parvum. J. Parasitol. 81, 429–433 (1995).
  Article CAS PubMed Google Scholar
• Danenberg, H. D., Ben-Yehuda, A., Zakay-Rones, Z. & Friedman, G. Dehydroepiandrosterone (DHEA) treatment reverses the impaired immune response of old mice to influenza vaccination and protects from influenza infection. Vaccine 13, 1445–1448 (1995).
  Article CAS PubMed Google Scholar
• Loria, R. M. & Padgett, D. A. Androstenediol regulates systemic resistance against lethal infections in mice. Ann. N Y Acad. Sci. 685, 293–295 (1993).
  Article CAS PubMed Google Scholar
• Loria, R. M. & Padgett, D. A. Androstenediol regulates systemic resistance against lethal infections in mice. Arch Virol. 127, 103–115 (1992).
  Article CAS PubMed Google Scholar
• Kornbluth, A. What happened to drug trials in ulcerative colitis? Problems, PPARs, placebos and (possible) progress. Am. J. Gastroenterol. 96, 3232–3234 (2001).
  Article CAS PubMed Google Scholar
• Lewis, J. D. et al. An open-label trial of the PPAR-γ ligand rosiglitazone for active ulcerative colitis. Am. J. Gastroenterol. 96, 3323–3328 (2001).
  CAS PubMed Google Scholar
• Tan, M. H. Current treatment of insulin resistance in type 2 diabetes mellitus. Int J Clin Pract Suppl. 54–62 (2000).
• Molavi, B., Rasouli, N. & Mehta, J. L. Peroxisome proliferator-activated receptor ligands as antiatherogenic agents: panacea or another Pandora's box? J. Cardiovasc. Pharmacol. Ther. 7, 1–8 (2002).
  Article CAS PubMed Google Scholar
• Robins, S. J. PPARα ligands and clinical trials: cardiovascular risk reduction with fibrates. J. Cardiovasc. Risk 8, 195–201 (2001).
  Article CAS PubMed Google Scholar
• Palakurthi, S. S., Aktas, H., Grubissich, L. M., Mortensen, R. M. & Halperin, J. A. Anticancer effects of thiazolidinediones are independent of peroxisome proliferator-activated receptor-γ and mediated by inhibition of translation initiation. Cancer Res. 61, 6213–6218 (2001).
  CAS PubMed Google Scholar
• Funk, C. D. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science 294, 1871–1875 (2001).
  Article CAS PubMed Google Scholar
• Tolon, R. M., Castillo, A. I., Jimenez-Lara, A. M. & Aranda, A. Association with Ets-1 causes ligand- and AF2-independent activation of nuclear receptors. Mol. Cell. Biol. 20, 8793–8802 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Yi, Y W. et al. Gadd45 family proteins are coactivators of nuclear hormone receptors. Biochem. Biophys. Res. Commun. 272, 193–198 (2000).
  Article CAS PubMed Google Scholar