Fli-1 transcription factor regulates the expression of caspase-1 in lung pericytes. (April 2019)

• Record Type: Journal Article
• Authors: Li, Pengfei; Goodwin, Andrew J.; Cook, James A.; Halushka, Perry V.; Zhang, Xian K.; Fan, Hongkuan
• Is Part Of: Molecular immunology. Volume 108(2019:Apr.)
• Page Start: 1
• Page End: 7
• Publication Date: 2019-04
• Subjects: Fli-1 -- Pericytes -- Caspase-1; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2019.02.003
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: Fli-1 induces caspase-1 and IL-18 expression in cultured lung pericytes. Knockdown of Fli-1 inhibits intracellular LPS-induced caspase-1 and IL-18 expression. Fli-1 transcription factor drives transcription of the murine caspase-1 promoter. Abstract: Our previous data demonstrated that Friend leukemia virus integration 1 (Fli-1), an ETS transcription factor, governs pericyte loss and vascular dysfunction in cecal ligation and puncture-induced murine sepsis by regulating essential pyroptosis markers including caspase-1. However, whether Fli-1 regulates caspase-1 expression levels in vitro and how Fli-1 regulates caspase-1 remain unknown. Our present work further demonstrated that overexpressed Fli-1 significantly increased caspase-1 and IL-18 expression levels in cultured mouse lung pericytes. Bacterial outer membrane vesicles (OMVs) have been found to induce cell pyroptosis through transferring LPS intracellularly. Using OMVs to induce an in vitro model of pyroptosis, we observed that OMVs significantly increased protein levels of Fli-1 in mouse lung pericytes. Furthermore, knockdown of Fli-1 by siRNA blocked OMVs-induced caspase-1, caspase-11 and IL-18 expression levels. As caspase-1 was predicted as a potential target of Fli-1, we cloned murine caspase-1 promoter into a luciferase construct. Our data demonstrate for the first time that Fli-1 regulates caspase-1 expression by directly binding to its promoter regions measured by chromatin immunoprecipitation (ChIP) assay and luciferase reporter system. In summary, our findings demonstrated a novel role and mechanism of Fli-1 in regulating caspase-1 expression in lung pericytes.