the ppar- agonist 15-deoxy--prostaglandin attenuates microglial production of il-12 family cytokines potential relevance to alzheimers diseaseppar -受体激动剂15-deoxyu2014u2014前列腺素变弱小胶质细胞因子白介素家族的生产潜力与阿尔茨海默病之间的关系.pdfVIP

Hindawi Publishing Corporation PPAR Research Volume 2008, Article ID 349185, 9 pages doi:10.1155/2008/349185 Research Article The PPAR-γ Agonist 15-Deoxy-Δ12,14-Prostaglandin J2 Attenuates Microglial Production of IL-12 Family Cytokines: Potential Relevance to Alzheimer’s Disease Jihong Xu,1 Steven W. Barger,2 and Paul D. Drew1 1 Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, AR 72205, USA 2 Department of Geriatrics, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, AR 72205, USA Correspondence should be addressed to Paul D. Drew, drewpauld@ Received 22 March 2008; Accepted 22 April 2008 Recommended by Michael Racke Accumulation of amyloid-β peptide (Aβ ) appears to contribute to the pathogenesis of Alzheimer’s disease (AD). Therapeutic hope for the prevention or removal of Aβ deposits has been placed in strategies involving immunization against the Aβ peptide. Initial Aβ immunization studies in animal models of AD showed great promise. However, when this strategy was attempted in human subjects with AD, an unacceptable degree of meningoencephalitis occurred. It is generally believed that this adverse outcome resulted from a T-cell response to Aβ . Specifically, CD4+ Th1 and Th17 cells may contribute to severe CNS inflammation and limit the utility of Aβ immunization in the treatment of AD. Interleukin (IL)-12 and IL-23 play critical roles in the development of Th1 and Th17 cells, respectively. In the present study, Aβ 1-42 synergistically elevated the expression of IL-12 and IL-23 triggered 12,14