RESUMO
The mycobacteriophage Pinkcreek (C1 subcluster) was extracted from soil collected on the Dr. Norman C. Francis Parkway Bike Trail in New Orleans, Louisiana. It is a member of the family Myoviridae and infects Mycobacterium smegmatis mc2155. The Pinkcreek genome is 153,184 bp and contains 216 predicted protein-coding genes, 29 tRNAs, and 1 transfer-messenger RNA.
RESUMO
The accumulation of amyloid beta (Aß) plaques in the brain is a hallmark of Alzheimer's disease (AD) pathology. Microglial activation-mediated neuroinflammation has been implicated in the pathogenesis of AD and the expression levels of interleukin-6 (IL-6) were increased in the brains of AD patients. However, the mechanisms by which IL-6 expression is regulated in human microglia are incompletely understood. Here, we show that Aß1-40 oligomers (Aß40) dose-dependently stimulate IL-6 expression in HMC3 human microglial cells. Treatment with Aß40 promotes the transcription of IL-6 and tumor necrosis factor α (TNFα) mRNAs in both HMC3 and THP-1 cells. Mechanistic studies reveal that Aß40-induced increase of IL-6 secretion is associated with the activation of p38 mitogen-activated protein kinase (p38 MAPK). Inhibition of p38 MAPK by BIRB 796 or SB202190 abrogates Aß40-induced increase of IL-6 production. Through analyzing brain specimens, we found that the immunoreactivity for IL-6 and phosphorylated (the activated form) p38 MAPK was markedly higher in microglia of AD patients than in age-matched control subjects. Moreover, our studies identified the co-localization of IL-6 with phosphorylated p38 MAPK in microglia in the cortices of AD patients. Taken together, these results indicate that p38 MAPK is a major regulator of Aß-induced IL-6 production in human microglia, which suggests that targeting p38 MAPK may represent a new approach to ameliorate Aß accumulation-induced neuroinflammation in AD.
Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Humanos , Interleucina-6/metabolismo , Microglia/metabolismo , Placa Amiloide/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
The mycobacteriophages JeTaime (E cluster) and Luna22 (Q cluster) were isolated from soil in Providence, Rhode Island, and Charleston, South Carolina, respectively, using a Mycobacterium smegmatis mc2 155 host. The genome of JeTaime is 75,099 bp (142 predicted genes), and that of Luna22 is 53,730 bp (87 predicted genes). Both phages exhibit Siphoviridae morphology.
