Amelioration of age-related inflammation and oxidative stress by PPARgamma activator: suppression of NF-kappaB by 2,4-thiazolidinedione.

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of transcription factors and are key regulators in various pathophysiological processes related to energy metabolism including lipid and carbohydrate metabolism and inflammation. PPARgamma signaling pathways are reported to exert anti-inflammatory effects by inhibition of NF-kappaB. We previously reported that age-related oxidative stress and inflammatory reactions cause reduced PPARgamma during the aging process. In present study, we investigated the action of 2,4-thiazolidinedione (2,4-TZD), a well-known PPARgamma activator, on aging process using kidneys from Fischer 344 rats, young (9-month-old), old (22-month-old) and old-2,4-TZD fed (4 mg/kg for 10 days). The results showed that the 2,4-TZD treatment brought about several major changes, decrease of: (1) age-related oxidative stress; (2) p65 translocation and NF-kappaB binding activity; (3) NF-kappaB-regulated gene expression, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and inflammatory mediators such as interleukin-1beta (IL-1beta), IL-6, adhesion molecules, VCAM-1 and P-selectin; and (4) age-related disturbance of the redox-status. Therefore, we concluded that 2,4-TZD exerted significant anti-oxidative and anti-inflammatory effects in aged rats, most likely by its ability to attenuate oxidative stress. We propose that 2,4-TZD or other potent PPARgamma activators may be useful in the therapy against age-related inflammation.