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Western blotting and real-time PCR (RT-PCR) were used to detect the protein and mRNA levels, respectively. IL-1\u03b2 and IL-18 levels were measured by ELISA. ASM assay kit and immunofluorescence were used to detect ASM activity and Cer content.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Imipramine, a well-known inhibitor of ASM, significantly inhibited LPS\/ATP-induced activity of ASM and the consequent accumulation of Cer. Additionally, imipramine suppressed the LPS\/ATP-induced expression of thioredoxin interacting protein (TXNIP), NLRP3, caspase-1, IL-1\u03b2, and IL-18 at the protein and mRNA level. Interestingly verapamil, a TXNIP inhibitor, suppressed LPS\/ATP-induced activation of TXNIP\/NLRP3 inflammasome but did not affect LPS\/ATP-induced ASM activation and Cer formation. TXNIP siRNA and verapamil inhibited C2-Cer-induced upregulation of TXNIP and activation of the NLRP3 inflammasome. In addition, the pretreatment of cells with sulfo-N-succinimidyl oleate (SSO), an irreversible inhibitor of the scavenger receptor CD36, blocked Cer-induced upregulation of nuclear factor-\u03baB (NF-\u03baB) activity, TXNIP expression, and NLRP3 inflammasome activation. Inhibition of NF-\u03baB activation by SN50 prevented Cer-induced upregulation of TXNIP and activation of the NLRP3 inflammasome but did not affect CD36 expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study demonstrated that the ASM\/Cer\/TXNIP signaling pathway is involved in NLRP3 inflammasome activation. The results documented that the CD36-dependent NF-\u03baB-TXNIP signaling pathway plays an essential role in the Cer-induced activation of NLRP3 inflammasomes in macrophages.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12944-021-01446-4","type":"journal-article","created":{"date-parts":[[2021,2,21]],"date-time":"2021-02-21T01:03:18Z","timestamp":1613869398000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Role of ASM\/Cer\/TXNIP signaling module in the NLRP3 inflammasome activation"],"prefix":"10.1186","volume":"20","author":[{"given":"Jianjun","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yining","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyu","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youjin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gengyun","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,21]]},"reference":[{"key":"1446_CR1","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1038\/nature01320","volume":"420","author":"C Nathan","year":"2002","unstructured":"Nathan C. 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