NDLI: Molecular mechanisms responsible for the selective and low-grade induction of proinflammatory mediators in murine macrophages by lipopolysaccharide.

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Molecular mechanisms responsible for the selective and low-grade induction of proinflammatory mediators in murine macrophages by lipopolysaccharide.

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Molecular mechanisms responsible for the selective and low-grade induction of proinflammatory mediators in murine macrophages by lipopolysaccharide.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Capelluto, Daniel G. S. Maitra, Urmila Deng, Hui Baker, Bianca Glaros, Trevor Li, Zihai Li, Liwu
Description	Country affiliation: United States Author Affiliation: Maitra U ( Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.)
Abstract	Low-dose endotoxemia is prevalent in humans with adverse health conditions, and it correlates with the pathogenesis of chronic inflammatory diseases such as atherosclerosis, diabetes, and neurologic inflammation. However, the underlying molecular mechanisms are poorly understood. In this study, we demonstrate that subclinical low-dose LPS skews macrophages into a mild proinflammatory state, through cell surface TLR4, IL-1R-associated kinase-1, and the Toll-interacting protein. Unlike high-dose LPS, low-dose LPS does not induce robust activation of NF-κB, MAPKs, PI3K, or anti-inflammatory mediators. Instead, low-dose LPS induces activating transcription factor 2 through Toll-interacting protein-mediated generation of mitochondrial reactive oxygen species, allowing mild induction of proinflammatory mediators. Low-dose LPS also suppresses PI3K and related negative regulators of inflammatory genes. Our data reveal novel mechanisms responsible for skewed and persistent low-grade inflammation, a cardinal feature of chronic inflammatory diseases.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1200857
Journal	The Journal of Immunology
Issue Number	2
Volume Number	189
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-07-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Gene Expression Regulation Immunology Inflammation Mediators Metabolism Lipopolysaccharides Toxicity Macrophages Pathology Activating Transcription Factor 2 Physiology Animals Bone Marrow Cells Cells, Cultured Dose-response Relationship, Immunologic Interleukin-1 Receptor-associated Kinases Genetics Intracellular Fluid Intracellular Signaling Peptides And Proteins Mice Mice, Inbred C57bl Mice, Knockout Mitochondria Phosphatidylinositol 3-kinase Antagonists & Inhibitors Reactive Oxygen Species Signal Transduction Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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