Browsing by Subject "Leukotriene B4"

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    Leukotriene B4 as a Potential Therapeutic Target for the Treatment of Metabolic Disorders
    (Frontiers Media, 2015-10-08) Filgueiras, Luciano Ribeiro; Serezani, C. Henrique; Jancar, Sonia; Department of Microbiology & Immunology, IU School of Medicine
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    Leukotriene B4 enhances the generation of proinflammatory microRNAs to promote MyD88-dependent macrophage activation
    (The American Association of Immunologists, 2014-03-01) Wang, Zhuo; Filgueiras, Luciano; Wang, Suonjan; Serezani, Ana Paula Moreira; Peters-Golden, Marc; Jancar, Sonia; Serezani, C. Henrique; Department of Microbiology and Immunology, IU School of Medicine
    MicroRNAs are known to control TLR activation in phagocytes. We have shown that leukotriene (LT) B4 (LTB4) positively regulates macrophage MyD88 expression by decreasing suppressor of cytokine signaling-1 (SOCS-1) mRNA stability. In this study, we investigated the possibility that LTB4 control of MyD88 expression involves the generation of microRNAs. Our data show that LTB4, via its receptor B leukotriene receptor 1 (BLT1) and Gαi signaling, increased macrophage expression of inflammatory microRNAs, including miR-155, miR-146b, and miR-125b. LTB4-mediated miR-155 generation was attributable to activating protein-1 activation. Furthermore, macrophage transfection with antagomirs against miR-155 and miR-146b prevented both the LTB4-mediated decrease in SOCS-1 and increase in MyD88. Transfection with miR-155 and miR-146b mimics decreased SOCS-1 levels, increased MyD88 expression, and restored TLR4 responsiveness in both wild type and LT-deficient macrophages. To our knowledge, our data unveil a heretofore unrecognized role for the GPCR BLT1 in controlling expression of microRNAs that regulate MyD88-dependent activation of macrophages.
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    Too much of a good thing: How modulating LTB4 actions restore host defense in homeostasis or disease
    (Elsevier, 2017-10) Brandt, Stephanie L.; Serezani, C. Henrique; Microbiology and Immunology, School of Medicine
    The ability to regulate inflammatory pathways and host defense mechanisms is critical for maintaining homeostasis and responding to infections and tissue injury. While unbalanced inflammation is detrimental to the host; inadequate inflammation might not provide effective signals required to eliminate pathogens. On the other hand, aberrant inflammation could result in organ damage and impair host defense. The lipid mediator leukotriene B4 (LTB4) is a potent neutrophil chemoattractant and recently, its role as a dominant molecule that amplifies many arms of phagocyte antimicrobial effector function has been unveiled. However, excessive LTB4 production contributes to disease severity in chronic inflammatory diseases such as diabetes and arthritis, which could potentially be involved in poor host defense in these groups of patients. In this review we discuss the cellular and molecular programs elicited during LTB4 production and actions on innate immunity host defense mechanisms as well as potential therapeutic strategies to improve host defense.