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Gut 55:1341-1349 doi:10.1136/gut.2006.093484
  • Recent advances in basic science

PPARγ as a new therapeutic target in inflammatory bowel diseases

  1. L Dubuquoy1,
  2. C Rousseaux1,
  3. X Thuru1,
  4. L Peyrin-Biroulet1,
  5. O Romano1,
  6. P Chavatte2,
  7. M Chamaillard1,
  8. P Desreumaux1
  1. 1INSERM U795, Lille, France, Univ Lille 2, France, and CHRU Lille, Hôpital Huriez, Service des Maladies de l’Appareil Digestif et de la Nutrition, Lille, France
  2. 2Laboratoire de Chimie Thérapeutique, EA1043, Faculté des Sciences Pharmaceutiques et Biologiques, Lille Cedex, France
  1. Correspondence to:
    Dr P Desreumaux
    INSERM U795 ex E114, Clinique des Maladies de l’Appareil Digestif et de la Nutrition, Hôpital Swynghedauw, rue A Verhaeghe, F-59037 Lille Cedex, France; pdesreumaux{at}chru-lille.fr

    SUMMARY

    The peroxisome proliferator activated receptor γ (PPARγ) is a nuclear receptor highly expressed in the colon and playing a key role in bacterial induced inflammation. Regulation of colon inflammation by this receptor has been well demonstrated in many experimental models of colitis but also in patients with ulcerative colitis, characterised by impaired expression of PPARγ confined to their colon epithelial cells. Recent data showing that PPARγ was the major functional receptor mediating the common aminosalicylate activities in inflammatory bowel diseases (IBD) have also reinforced the roles of this receptor in the control of intestinal inflammation. The aims of this review are to discuss the potential roles of PPARγ in the physiopathology of IBD, as well as the emerging therapeutic strategies targeting this receptor.

    INTRODUCTION

    Current evidence suggests that Crohn’s disease (CD) and ulcerative colitis (UC) result from a complex interplay between genetic and environmental factors, leading to an abnormal innate and adaptive immune response of the gut directed against luminal constituents in genetically determined patients. Identification of cytoplasmic receptors of bacterial peptidoglycan, namely nucleotide oligomerisation domain (NOD)2/caspase recruitment domain (CARD)15 and NOD1/CARD4, as CD susceptibility genes reinforced the pivotal role of the interactions between enteric microbes and the intestinal immune system in the physiopathology of IBD.1–3 Furthermore, recent advances in our laboratory and others also indicate the involvement of another key receptor, PPARγ, which regulates colon inflammation. This represents a new target in the development of therapeutic molecules in IBD.

    PPARγ is a nuclear receptor discovered in mammals in 1993 as an orphan receptor.4 Until recently, PPARγ was known as a receptor mainly expressed by adipose tissue and involved in the regulation of insulin resistance. PPARγ is activated by antidiabetic thiazolidinedione drugs.5 In 1998, the first studies were published reporting a potential link between this receptor and …