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Leukotriene B4 licenses inflammasome activation to enhance skin host defense

dc.contributor.authorSalina, Ana Carolina Guerta [UNESP]
dc.contributor.authorBrandt, Stephanie L.
dc.contributor.authorKlopfenstein, Nathan
dc.contributor.authorBlackman, Amondrea
dc.contributor.authorBazzano, Júlia Miranda Ribeiro
dc.contributor.authorSá-Nunes, Anderson
dc.contributor.authorByers-Glosson, Nicole
dc.contributor.authorBrodskyn, Claudia
dc.contributor.authorTavares, Natalia Machado
dc.contributor.authorSilva, Icaro Bonyek Santos Da
dc.contributor.authorMedeiros, Alexandra I. [UNESP]
dc.contributor.authorHenrique Serezani, C.
dc.contributor.institutionVanderbilt University Medical Center
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionIndiana University School of Medicine
dc.contributor.institutionFIOCRUZ
dc.date.accessioned2021-06-25T10:46:12Z
dc.date.available2021-06-25T10:46:12Z
dc.date.issued2020-12-01
dc.description.abstractThe initial production of inflammatory mediators dictates host defense as well as tissue injury. Inflammasome activation is a constituent of the inflammatory response by recognizing pathogen and host-derived products and eliciting the production of IL-1β and IL-18 in addition to inducing a type of inflammatory cell death termed “pyroptosis.” Leukotriene B4 (LTB4) is a lipid mediator produced quickly (seconds to minutes) by phagocytes and induces chemotaxis, increases cytokine/chemokine production, and enhances antimicrobial effector functions. Whether LTB4 directly activates the inflammasome remains to be determined. Our data show that endogenously produced LTB4 is required for the expression of pro-IL-1β and enhances inflammasome assembly in vivo and in vitro. Furthermore, LTB4-mediated Bruton’s tyrosine kinase (BTK) activation is required for inflammasome assembly in vivo as well for IL-1β–enhanced skin host defense. Together, these data unveil a new role for LTB4 in enhancing the expression and assembly of inflammasome components and suggest that while blocking LTB4 actions could be a promising therapeutic strategy to prevent inflammasome-mediated diseases, exogenous LTB4 can be used as an adjuvant to boost inflammasome-dependent host defense.en
dc.description.affiliationDepartment of Medicine Division of Infectious Diseases Vanderbilt University Medical Center
dc.description.affiliationDepartment of Biological Sciences School of Pharmaceutical Sciences São Paulo State University (UNESP)
dc.description.affiliationDepartment of Biochemistry and Immunology Faculty of Medicine of Ribeirão Preto University of São Paulo
dc.description.affiliationDepartment of Microbiology and Immunology Indiana University School of Medicine
dc.description.affiliationVanderbilt Institute of Infection Immunology and Inflammation Vanderbilt University Medical Center
dc.description.affiliationDepartment of Immunology Institute of Biomedical Sciences University of São Paulo
dc.description.affiliationOswaldo Cruz Foundation Gonçalo Moniz Institute FIOCRUZ
dc.description.affiliationDepartment of Pathology Microbiology and Immunology Vanderbilt University Medical Center
dc.description.affiliationVanderbilt Center for Immunobiology Vanderbilt University Medical Center
dc.description.affiliationUnespDepartment of Biological Sciences School of Pharmaceutical Sciences São Paulo State University (UNESP)
dc.format.extent30619-30627
dc.identifierhttp://dx.doi.org/10.1073/pnas.2002732117
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, v. 117, n. 48, p. 30619-30627, 2020.
dc.identifier.doi10.1073/pnas.2002732117
dc.identifier.issn1091-6490
dc.identifier.issn0027-8424
dc.identifier.scopus2-s2.0-85097210640
dc.identifier.urihttp://hdl.handle.net/11449/206930
dc.language.isoeng
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America
dc.sourceScopus
dc.subjectInflammasome | leukotriene | skin | innate immunity
dc.titleLeukotriene B4 licenses inflammasome activation to enhance skin host defenseen
dc.typeArtigo
unesp.departmentCiências Biológicas - FCFpt

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