A chronic inflammatory response possibly mediated by Amyloid beta (A beta) is believed to be a major factor in the pathology of Alzheimer's disease (AD). Studies suggest that the mediators of the inflammatory response, which might contribute to brain damage, involve cytokines, such as IL-1 beta. IL-1 beta could play an important part in the development of pathologic conditions. There is also an endogenous interleukin-1 receptor antagonist (IL-1RA) in IL-1 family, which could prevent the actions of IL-1 beta by competing for receptor binding without inducing any signal transduction. Therefore, the balance of IL-1 beta vs IL-1RA is a critical parameter in determining not only whether excessive host inflammation will occur, but also the degree of subsequent host cell damage and associated toxicity. In our previous study, it has been determined that the anti-inflammatory action of Gossypium herbaceam L. extracts (GHE) was involved in its neuroprotection. However, the effects of GHE on IL-1 beta and IL-1RA have not been clearly defined in the experimental rat model of AD induced by A beta. Therefore, the current study is performed to evaluate whether GHE could affect the disequilibrium of IL-1RA/IL-1 beta ratio in the hippocampus of rats after A beta treatment. Subsequently, we further identify that GHE could efficaciously promote Akt and GSK3 beta phosphorylation, and thereby contribute to IL-1 beta release decrease as well as a concurrent increase in the level of IL-1RA through NF-kappa B and MAPK pathways. As a consequence, GHE is potentially beneficial to maintain the endogenous IL-1RA/IL-1 beta balance in the hippocampus of rats and it might be a potential agent to ameliorate inflammatory process in AD.
Peking Union Med Coll, Dept Pharmacol, Sch Basic Med, Beijing 100005, Peoples R China;Chinese Acad Med Sci, Inst Basic Med Sci, Beijing 100005, Peoples R China;Chinese Acad Med Sci, Inst Mat Med, Beijing 100050, Peoples R China;Peking Union Med Coll, Beijing 100050, Peoples R China;Chinese Acad Sci, Xinjiang Tech Inst Phys & Chem, Urumqi 830011, Peoples R China;Univ Prince Edward Isl, AVC, Dept Biomed Sci, Charlottetown, PE C1A 4P3, Canada;Canada Natl Res Inst Nutrisci & Hlth, Charlottetown, PE C1A 4P3, Canada
Ji Chao,Song Cai,Aisa Haji Akber,et al. Gossypium herbaceam L. Extracts Ameliorate Disequilibrium of IL-1RA/IL-1 beta Ratio to Attenuate Inflammatory Process induced by Amyloid beta in Rats[J]. CURRENT ALZHEIMER RESEARCH,2012,9(8):953-961.