Increasing Autophagy ameliorate all-trans-retinal-activated NLRP3 Inflammasome 2 in human THP-1 macrophage cells

Increasing Autophagy ameliorate all-trans-retinal-activated NLRP3 Inflammasome 2 in human THP-1 macrophage cells | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Increasing Autophagy ameliorate all-trans-retinal-activated NLRP3 Inflammasome 2 in human THP-1 macrophage cells Qingqing Xia, Lvxing Huang, Hengyi Chen, Yingying Zhou, Lingmin Zhang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-797831/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Profound inflammation that mediated by innate immune sensors can be observed in retina, and is considered to play an important role in the pathogenesis of all-trans-retinal (atRAL)-caused retinal degeneration. However, the underlying mechanism remains elusive. Methods Cell viability was detected with Cell Counting Kit-8 (CCK-8). The concentration of IL-1β was evaluated using IL-1β ELISA Kits. The levels of autophagy-related proteins were measured by Western blotting. The measurement of autophagic flux was performed with virus vectors packing tandem monomeric mCherry-eGFP-tagged LC3B. Results We focused on studying the effects of atRAL on macrophage cell line THP-1 and determining the underlying signal pathway through pharmacological and genetical manipulation. We first found the maturation and release of IL-1β was regulated by the activation of NLRP3 inflammasome. We secondly found that mitochondria-associated reactive oxygen species (ROS) were involved in the regulation of NLRP3 inflammasome activation and caspase 1 cleavage. Finally, we found that atRAL functionally activated autophagy in THP-1 cells, and atRAL-caused NLRP3 inflammasome activation is suppressed by autophagy. Overall, our results show atRAL simultaneously activates NLRP3 inflammasome and autophagy in THP-1 cells, and increasing autophagy leads to the inhibition of the excessive activation of NLRP3 inflammasome. Our study provides new insight into the pathogenesis of aging related retina degeneration. Laboratory Diagnostics Forensic Medicine Macroeconomics Autophagy NLRP3 Inflammasome THP-1 Macrophage Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-797831","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":44903449,"identity":"bbb67703-12fe-4d75-b5cc-e3383648068a","order_by":0,"name":"Qingqing Xia","email":"","orcid":"","institution":"Department of Laboratory Medicine, Huangyan Hospital of Wenzhou Medical University, Taizhou First People's Hospital, Taizhou, Zhejiang 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However, the underlying mechanism remains elusive. \u003c/p\u003e\u003cp\u003eMethods\u003c/p\u003e\u003cp\u003eCell viability was detected with Cell Counting Kit-8 (CCK-8). The concentration of IL-1β was evaluated using IL-1β ELISA Kits. The levels of autophagy-related proteins were measured by Western blotting. The measurement of autophagic flux was performed with virus vectors packing tandem monomeric mCherry-eGFP-tagged LC3B. \u003c/p\u003e\u003cp\u003eResults\u003c/p\u003e\u003cp\u003eWe focused on studying the effects of atRAL on macrophage cell line THP-1 and determining the underlying signal pathway through pharmacological and genetical manipulation. We first found the maturation and release of IL-1β was regulated by the activation of NLRP3 inflammasome. We secondly found that mitochondria-associated reactive oxygen species (ROS) were involved in the regulation of NLRP3 inflammasome activation and caspase 1 cleavage. Finally, we found that atRAL functionally activated autophagy in THP-1 cells, and atRAL-caused NLRP3 inflammasome activation is suppressed by autophagy. 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