Pyroptosis is a recently discovered inflammatory form of programmed cell death which is mostly triggered by infection with intracellular pathogens and critically contributes to inflammation. Mitigating pyroptosis may be a potential therapeutic target in inflammatory diseases. However, small chemicals to reduce pyroptosis is still elusive. In the present study, we screened 155 chemicals from a microbial natural product library and found Geldanamycin, an HSP90 inhibitor, profoundly rescued THP-1 cells from pyroptosis induced by LPS plus Nigericin treatment. Consistently, other HSP90 inhibitors, including Radicicol, 17-DMAG and 17-AAG, all ameliorated pyroptosis in THP-1 cells by suppressing the inflammasome/Caspase-1/GSDMD signal pathway in pyroptosis. HSP90 inhibition compromised the protein stability of NLRP3, a critical component of the inflammasome. Moreover, up-regulated HSP70 may also contribute to this effect. HSP90 inhibition may thus be a potential therapeutic strategy in the treatment of inflammatory diseases in which pyroptosis plays a role.
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Cover Image
Cover Image
Chakraborti and colleagues (pp. 1345–1362) report the identification of bacteriophage ƛ NinH as a structural and functional analog of the bacterial nucleoid-associated protein Fis. NinH may influence phage excision-integration reactions or bacterial gene expression by competing with Fis for binding sites. The cover image shows Fis bound to DNA with homology to NinH highlighted. NinH binds and bends DNA with a preference for a 15 bp palindromic motif that is closely related to that recognised by E. coli Fis.
Heat shock protein 90 inhibitors suppress pyroptosis in THP-1 cells
Zhou Zhou, Xiuzhen Li, Yisong Qian, Cynthia Liu, Xiaotian Huang, Mingui Fu; Heat shock protein 90 inhibitors suppress pyroptosis in THP-1 cells. Biochem J 30 October 2020; 477 (20): 3923–3934. doi: https://doi.org/10.1042/BCJ20200351
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