| First Author | Wu Z | Year | 2013 |
| Journal | Neurobiol Aging | Volume | 34 |
| Issue | 12 | Pages | 2715-25 |
| PubMed ID | 23831373 | Mgi Jnum | J:327393 |
| Mgi Id | MGI:6837018 | Doi | 10.1016/j.neurobiolaging.2013.05.018 |
| Citation | Wu Z, et al. (2013) Differential pathways for interleukin-1beta production activated by chromogranin A and amyloid beta in microglia. Neurobiol Aging 34(12):2715-25 |
| abstractText | Although chromogranin A (CGA) is frequently present in Alzheimer's disease (AD), senile plaques associated with microglial activation, little is known about basic difference between CGA and fibrillar amyloid-beta (fAbeta) as neuroinflammatory factors. Here we have compared the interleukin-1beta (IL-1beta) production pathways by CGA and fAbeta in microglia. In cultured microglia, production of IL-1beta was induced by CGA, but not by fAbeta. CGA activated both nuclear factor-kappaB (NF-kappaB) and pro-caspase-1, whereas fAbeta activated pro-caspase-1 only. For the activation of pro-caspase-1, both CGA and fAbeta needed the enzymatic activity of cathepsin B (CatB), but only fAbeta required cytosolic leakage of CatB and the NLRP3 inflammasome activation. In contrast, fAbeta induced the IL-1beta secretion from microglia isolated from the aged mouse brain. In AD brain, highly activated microglia, which showed intense immunoreactivity for CatB and IL-1beta, surrounded CGA-positive plaques more frequently than Abeta-positive plaques. These observations indicate differential pathways for the microglial IL-1beta production by CGA and fAbeta, which may aid in better understanding of the pathological significance of neuroinflammation in AD. |
