Leukotriene B4 licenses inflammasome activation to enhance skin host defense
dc.contributor.author | Salina, Ana Carolina Guerta [UNESP] | |
dc.contributor.author | Brandt, Stephanie L. | |
dc.contributor.author | Klopfenstein, Nathan | |
dc.contributor.author | Blackman, Amondrea | |
dc.contributor.author | Bazzano, Júlia Miranda Ribeiro | |
dc.contributor.author | Sá-Nunes, Anderson | |
dc.contributor.author | Byers-Glosson, Nicole | |
dc.contributor.author | Brodskyn, Claudia | |
dc.contributor.author | Tavares, Natalia Machado | |
dc.contributor.author | Silva, Icaro Bonyek Santos Da | |
dc.contributor.author | Medeiros, Alexandra I. [UNESP] | |
dc.contributor.author | Henrique Serezani, C. | |
dc.contributor.institution | Vanderbilt University Medical Center | |
dc.contributor.institution | Universidade Estadual Paulista (Unesp) | |
dc.contributor.institution | Universidade de São Paulo (USP) | |
dc.contributor.institution | Indiana University School of Medicine | |
dc.contributor.institution | FIOCRUZ | |
dc.date.accessioned | 2021-06-25T10:46:12Z | |
dc.date.available | 2021-06-25T10:46:12Z | |
dc.date.issued | 2020-12-01 | |
dc.description.abstract | The 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.affiliation | Department of Medicine Division of Infectious Diseases Vanderbilt University Medical Center | |
dc.description.affiliation | Department of Biological Sciences School of Pharmaceutical Sciences São Paulo State University (UNESP) | |
dc.description.affiliation | Department of Biochemistry and Immunology Faculty of Medicine of Ribeirão Preto University of São Paulo | |
dc.description.affiliation | Department of Microbiology and Immunology Indiana University School of Medicine | |
dc.description.affiliation | Vanderbilt Institute of Infection Immunology and Inflammation Vanderbilt University Medical Center | |
dc.description.affiliation | Department of Immunology Institute of Biomedical Sciences University of São Paulo | |
dc.description.affiliation | Oswaldo Cruz Foundation Gonçalo Moniz Institute FIOCRUZ | |
dc.description.affiliation | Department of Pathology Microbiology and Immunology Vanderbilt University Medical Center | |
dc.description.affiliation | Vanderbilt Center for Immunobiology Vanderbilt University Medical Center | |
dc.description.affiliationUnesp | Department of Biological Sciences School of Pharmaceutical Sciences São Paulo State University (UNESP) | |
dc.format.extent | 30619-30627 | |
dc.identifier | http://dx.doi.org/10.1073/pnas.2002732117 | |
dc.identifier.citation | Proceedings of the National Academy of Sciences of the United States of America, v. 117, n. 48, p. 30619-30627, 2020. | |
dc.identifier.doi | 10.1073/pnas.2002732117 | |
dc.identifier.issn | 1091-6490 | |
dc.identifier.issn | 0027-8424 | |
dc.identifier.scopus | 2-s2.0-85097210640 | |
dc.identifier.uri | http://hdl.handle.net/11449/206930 | |
dc.language.iso | eng | |
dc.relation.ispartof | Proceedings of the National Academy of Sciences of the United States of America | |
dc.source | Scopus | |
dc.subject | Inflammasome | leukotriene | skin | innate immunity | |
dc.title | Leukotriene B4 licenses inflammasome activation to enhance skin host defense | en |
dc.type | Artigo | |
unesp.department | Ciências Biológicas - FCF | pt |