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https://www.arca.fiocruz.br/handle/icict/45771
LEUKOTRIENE B4 LICENSES INFLAMMASOME ACTIVATION TO ENHANCE SKIN HOST DEFENSE
Author
Affilliation
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN / São Paulo State University. School of Pharmaceutical Sciences. Department of Biological Sciences. Araraquara, SP, Brazil / University of São Paulo. Faculty of Medicine of Ribeirão Preto. Department of Biochemistry and Immunology. Ribeirão Preto, SP, Brazil.
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN / Indiana University School of Medicine. Department of Microbiology and Immunology,Indianapolis. IN.
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN / Vanderbilt University Medical Center. Vanderbilt Institute of Infection, Immunology and Inflammation. Nashville, TN.
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN.
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN.
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN / University of São Paulo. Institute of Biomedical Sciences. Department of Immunology. São Paulo, SP, Brazil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Bahia, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Bahia, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Bahia, Brasil.
São Paulo State University. School of Pharmaceutical Sciences. Department of Biological Sciences. Araraquara, SP, Brazil.
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN / Vanderbilt University Medical Center. Microbiology, and Immunology. Department of Pathology. Nashville, TN / Vanderbilt University Medical Center. Vanderbilt Institute of Infection, Immunology and Inflammation. Nashville, TN / Vanderbilt University Medical Center. Center for Immunobiology. Nashville, TN.
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN / Indiana University School of Medicine. Department of Microbiology and Immunology,Indianapolis. IN.
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN / Vanderbilt University Medical Center. Vanderbilt Institute of Infection, Immunology and Inflammation. Nashville, TN.
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN.
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN.
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN / University of São Paulo. Institute of Biomedical Sciences. Department of Immunology. São Paulo, SP, Brazil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Bahia, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Bahia, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Bahia, Brasil.
São Paulo State University. School of Pharmaceutical Sciences. Department of Biological Sciences. Araraquara, SP, Brazil.
Vanderbilt University Medical Center. Department of Medicine. Division of Infectious Diseases. Nashville, TN / Vanderbilt University Medical Center. Microbiology, and Immunology. Department of Pathology. Nashville, TN / Vanderbilt University Medical Center. Vanderbilt Institute of Infection, Immunology and Inflammation. Nashville, TN / Vanderbilt University Medical Center. Center for Immunobiology. Nashville, TN.
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.
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