Differential pathways for interleukin-1 beta production activated by chromogranin A and amyloid beta in microglia

作者：Wu Zhou^*; Sun Li; Hashioka Sadayuki; Yu Sheng; Schwab Claudia; Okada Ryo; Hayashi Yoshinori; McGeer Patrick L; Nakanishi Hiroshi

来源：Neurobiology of Aging, 2013, 34(12): 2715-2725.

DOI：10.1016/j.neurobiolaging.2013.05.018

• Alzheimer%26apos
• s disease
• Amyloid beta protein
• Cathepsin B
• Chromogranin A
• Interleukin-1 beta
• Microglia
• Nuclear factor-kappa B
• Toll-like receptor 4

Although chromogranin A (CGA) is frequently present in Alzheimer%26apos;s disease (AD), senile plaques associated with microglial activation, little is known about basic difference between CGA and fibrillar amyloid-beta (fA beta) as neuroinflammatory factors. Here we have compared the interleukin-1 beta (IL-1 beta) production pathways by CGA and fA beta in microglia. In cultured microglia, production of IL-1 beta was induced by CGA, but not by fA beta. CGA activated both nuclear factor-kappa B (NF-kappa B) and proecaspase-1, whereas fA beta activated proecaspase-1 only. For the activation of proecaspase-1, both CGA and fA beta needed the enzymatic activity of cathepsin B (CatB), but only fA beta required cytosolic leakage of CatB and the NLRP3 inflammasome activation. In contrast, fA beta induced the IL-1 beta secretion from microglia isolated from the aged mouse brain. In AD brain, highly activated microglia, which showed intense immunoreactivity for CatB and IL-1 beta, surrounded CGA-positive plaques more frequently than A beta-positive plaques. These observations indicate differential pathways for the microglial IL-1 beta production by CGA and fA beta, which may aid in better understanding of the pathological significance of neuroinflammation in AD.

• 出版日期2013-12