Soluble Aβ1-42 suppresses TNF-α and activates NLRP3 inflammasome in THP-1 macrophages.

Abstract

Deposition of amyloid-β in Alzheimer's disease is accompanied by chronic inflammation, which involves raised levels of pro-inflammatory cytokines TNF-α, IL-6 and IL-1β. However, the role of Aβ1-42 in the inflammatory process, before it gets deposited into aggregates has not been investigated thoroughly. Through this study, we are illustrating the dual role of soluble Aβ1-42 (sAβ1-42) in activating the NLRP3 inflammasome and simultaneously inhibiting TNF-α secretion. Our data suggested that the treatment of chronically induced THP-1 macrophages and N9 microglial cells with sAβ1-42 can suppress the major inflammatory cytokine TNF-α without affecting the level of IL-6. However, the activation of NLRP3 inflammasome was well evidenced by secretion of IL-1β, increased expression of NLRP3 and caspase-1, implicating sAβ1-42 in enhancing and suppressing one or other type of inflammation. Further investigation revealed that sAβ1-42 was able to severely abrogate the expression of NF-κB, p50 and restricting the translocation of NF-κB, p65 to nucleus by inhibiting phosphorylation of IκB-α in THP-1 macrophages. These data indicate that the sAβ1-42 may play a dual role during inflammatory process, wherein, it may be involved in protecting the cells from inflammatory damage due to TNF-α. This ability of sAβ1-42 might be playing some role in protecting the brain cells during the process of aging and Alzheimer's disease, where, chronic inflammatory environment plays a vital role.

• Authors: Mehak Gupta, Abubakar Wani, Aitizaz Ul Ahsan, Mani Chopra, Ram A Vishwakarma, Gurdarshan Singh, Ajay Kumar
• Journal: Cytokine (Cytokine) Vol. 111 Pg. 84-87 (11 2018) ISSN: 1096-0023 [Electronic] England
• PMID: 30125779 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018. Published by Elsevier Ltd.

Chemical References

• Amyloid beta-Peptides
• IL1B protein, human
• IL6 protein, human
• Inflammasomes
• Interleukin-1beta
• Interleukin-6
• NF-kappa B p50 Subunit
• NFKB1 protein, human
• NLR Family, Pyrin Domain-Containing 3 Protein
• NLRP3 protein, human
• Peptide Fragments
• RELA protein, human
• Transcription Factor RelA
• Tumor Necrosis Factor-alpha
• amyloid beta-protein (1-42)

Topics

• Alzheimer Disease (immunology, pathology)
• Amyloid beta-Peptides (immunology)
• Humans
• Inflammasomes (immunology)
• Interleukin-1beta (immunology)
• Interleukin-6 (immunology)
• Macrophages (immunology, pathology)
• Microglia (immunology, pathology)
• NF-kappa B p50 Subunit (immunology)
• NLR Family, Pyrin Domain-Containing 3 Protein (immunology)
• Peptide Fragments (immunology)
• Signal Transduction (immunology)
• Solubility
• THP-1 Cells
• Transcription Factor RelA (immunology)
• Tumor Necrosis Factor-alpha (immunology)