As one of the first-line medications for the treatment of IBD, 5-aminosalicylic acid (5-ASA) activates peroxisome proliferator-activated receptor gamma (PPAR<i>γ</i>) to attenuate colitis.
Therefore, PGD<sub>2</sub>-G could be one of the products from the COX-2/prostaglandin D synthase axis to exert beneficial effects in colitis.-Alhouayek, M., Buisseret, B., Paquot, A., Guillemot-Legris, O., Muccioli, G. G. The endogenous bioactive lipid prostaglandin D<sub>2</sub>-glycerol ester reduces murine colitis via DP1 and PPARγ receptors.
DSS-colitis mice received PPARγ agonists or vehicle daily by intrarectal administration starting 2 days before induction of colitis (preventive) or from days 3 to 8 (curative).
A novel pyrazole-containing indolizine derivative suppresses NF-κB activation and protects against TNBS-induced colitis via a PPAR-γ-dependent pathway.
Finally, the correlation between activation of PPARγ and attenuation of colitis, inhibition of IL-6 and TNF-α expressions, NF-κB-p65 acetylation and nuclear translocation, and up-regulation of SIRT1 expression by bergenin was validated in mice with DSS-induced colitis and/or LPS-stimulated macrophages.
While the clinical benefits of TZDs in treating metabolic disorders have been clearly demonstrated, new studies performed in animal models of colitis and in patients with ulcerative colitis have also revealed the key roles of PPARγ activation in the regulation of inflammation and immune response, notably in the colon through epithelial cells.
In mouse, we examined Vanin-1 expression in gut and feces during dextran sulfate sodium-induced colitis and assayed the effect of PPARg on Vanin-1 regulation.
Our findings showed that the lead compound, NSC61610, activated peroxisome proliferator-activated receptor gamma in a LANCL2- and adenylate cyclase/cAMP dependent manner in vitro and ameliorated experimental colitis by down-modulating colonic inflammatory gene expression and favoring regulatory T cell responses.
Mesenteric adipose tissue from rodent colitis and Crohn's disease is metabolically active and shows inflammation-driven regulation of PPARγ, FXR and leptin.
Moreover, macrophage PPAR-γ was required for accelerating pioglitazone-mediated recovery from dextran sodium sulfate (DSS) colitis, providing a cellular target for the anti-inflammatory effects of PPAR-γ agonists in IBD.
The peroxisome proliferator-activated receptor gamma (PPAR gamma) has been proposed as a key inhibitor of colitis through attenuation of nuclear factor kappa B (NF-kappa B) activity.