Wang, Longlong, Unterreiner, Adeline, Kapetanovic, Ronan, Aslani, Selma, Xiong, Yuan, Donovan, Katherine A., Farady, Christopher, Fischer, Eric S., Bornancin, Frederic and Matthias, Patrick (2024) HDAC6/aggresome processing pathway importance for inflammasome formation is context-dependent. The Journal of biological chemistry, 300 (2). p. 105638. ISSN 1083-351X

Abstract

The inflammasome is a large multiprotein complex that assembles in the cell cytoplasm in response to stress or pathogenic infection. Its primary function is to defend the cell and promote the secretion of pro-inflammatory cytokines, including IL-1β and IL-18. Previous research has shown that in immortalized bone marrow-derived macrophages (iBMDMs) inflammasome assembly is dependent on the deacetylase HDAC6 and the aggresome processing pathway (APP), a cellular pathway involved in the disposal of misfolded proteins. Here we used primary BMDMs from mice in which HDAC6 is ablated or impaired and found that inflammasome activation was largely normal. We also used human peripheral blood mononuclear cells and monocyte cell lines expressing a synthetic protein blocking the HDAC6-ubiquitin interaction and impairing the APP and found that inflammasome activation was moderately affected. Finally, we used a novel HDAC6 degrader and showed that inflammasome activation was partially impaired in human macrophage cell lines with depleted HDAC6. Our results therefore show that HDAC6 importance in inflammasome activation is context-dependent.

Item Type:	Article
Keywords:	Animals Humans Mice Cell Line Histone Deacetylase 6 Inflammasomes Interleukin-1beta Leukocytes, Mononuclear Macrophages NLR Family, Pyrin Domain-Containing 3 Protein Protein Transport
Date Deposited:	02 Apr 2024 00:45
Last Modified:	02 Apr 2024 00:46
URI:	https://oak.novartis.com/id/eprint/51124