Chen GY, Nunez GSterile inflammation: sensing and reacting to damage. Nat Rev Immunol 10:826-837

Department of Internal Medicine, Comprehensive Cancer Center, University of Michigan, Michigan 48109, USA.
Nature Reviews Immunology (Impact Factor: 34.99). 11/2010; 10(12):826-37. DOI: 10.1038/nri2873
Source: PubMed


Over the past several decades, much has been revealed about the nature of the host innate immune response to microorganisms, with the identification of pattern recognition receptors (PRRs) and pathogen-associated molecular patterns, which are the conserved microbial motifs sensed by these receptors. It is now apparent that these same PRRs can also be activated by non-microbial signals, many of which are considered as damage-associated molecular patterns. The sterile inflammation that ensues either resolves the initial insult or leads to disease. Here, we review the triggers and receptor pathways that result in sterile inflammation and its impact on human health.

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    • "In addition, as a result of hepatocytes damage, there are several sterile inflammatory signals in NAFL and NASH to provide the second signal for inflammasome activation. These sterile signals include but are not limited to fatty acids, uric acid, ATP, HMGB1 and likely other factors [7]. "
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    ABSTRACT: Upregulation of the inflammatory cascade is a major element both in the progression of steatohepatitis to severe alcoholic hepatitis as well as in the progression of NASH to advanced NASH with fibrosis. The mechanisms underpinning these changes are only partially understood. Activation of the inflammatory cascade requires multiple stimuli and in this report, we discuss the role of inflammasomes that activate IL-1β as well as the sterile and pathogen-derived danger signals that results in inflammasome activation and inflammation in alcoholic and non-alcoholic steatohepatitis. The dynamics of inflammasome activation, the cell types involved and the trigger signals appear to be somewhat different between ASH and NASH. Further studies are needed to dissect the pathology-related differences between these two major forms of steatohepatitis. Clinical and therapeutic implications of inflammasome activation in steatohepatitis are also discussed. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    Gastroentérologie Clinique et Biologique 07/2015; DOI:10.1016/j.clinre.2015.06.012 · 1.64 Impact Factor
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    • ", 2013 ) . DAMPs can activate membrane receptors like the receptor for advance glycation end product ( RAGE ) and pattern recognition receptors ( PRRs ) , such as toll - like receptors ( TLRs ) , NOD - like receptors ( NLRs ) , and puriner - gic receptors on target cells to initiate inflammatory responses ( Chen and Nunez , 2010 ) . Coincidently , TLRs and NLRs also rec - ognize pathogens and are a shared pathway for infectious and non - infectious inflammation ( Pradere et al . "
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    ABSTRACT: While chemotherapeutic agents have yielded relative success in the treatment of cancer, patients are often plagued with unwanted and even debilitating side-effects from the treatment which can lead to dose reduction or even cessation of treatment. Common side effects (symptoms) of chemotherapy include (i) cognitive deficiencies such as problems with attention, memory and executive functioning; (ii) fatigue and motivational deficit; and (iii) neuropathy. These symptoms often develop during treatment but can remain even after cessation of chemotherapy, severely impacting long-term quality of life. Little is known about the underlying mechanisms responsible for the development of these behavioral toxicities, however, neuroinflammation is widely considered to be one of the major mechanisms responsible for chemotherapy-induced symptoms. Here, we critically assess what is known in regards to the role of neuroinflammation in chemotherapy-induced symptoms. We also argue that, based on the available evidence, neuroinflammation is unlikely the only mechanism involved in the pathogenesis of chemotherapy-induced behavioral toxicities. We evaluate two other putative candidate mechanisms. To this end we discuss the mediating role of damage-associated molecular patterns (DAMPs) activated in response to chemotherapy-induced cellular damage. We also review the literature with respect to possible alternative mechanisms such as a chemotherapy-induced change in the bioenergetic status of the tissue involving changes in mitochondrial function in relation to chemotherapy-induced behavioral toxicities. Understanding the mechanisms that underlie the emergence of fatigue, neuropathy, and cognitive difficulties is vital to better treatment and long-term survival of cancer patients.
    Frontiers in Neuroscience 05/2015; 9. DOI:10.3389/fnins.2015.00131 · 3.66 Impact Factor
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    • "See also Figure S6. have been shown to be TLR4 ligands, as reviewed in Chen and Nuñ ez (2010). In summary, we demonstrate that (1) Gal3 can be actively released into the extracellular compartment by activated microglial cells, (2) Gal3 binds directly to TLR4 at physiological concentrations, (3) Gal3 itself activates TLR4 and is capable of activating surrounding microglia, (4) Gal3 amplifies the typical TLR4-dependent proinflammatory response, including caspase-mediated inflammation (Burguillos et al., 2011; Venero et al., 2011), and (5) TLR4/Gal3 interaction occurs in the brain of stroke patients as evidenced by FRET analysis. "
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    ABSTRACT: Graphical Abstract Highlights d Gal3 acts as an endogenous TLR4 ligand with a Kd value around 1 mM d Gal3 can initiate a TLR4-dependent inflammatory response in microglia d Gal3 is required for complete activation of TLR4 upon LPS treatment d Gal3-TLR4 interaction is confirmed in vivo and in stroke patients In Brief In this publication, Burguillos et al. demonstrate how galectin-3 (Gal3) released from reactive microglia cells can activate other surrounding immune cells in a paracrine manner by binding to and activating Toll-like receptor 4 (TLR4). This finding could explain the propagation of the inflammatory response once the initial stimulus is gone.
    Cell Reports 04/2015; 10(9):1626-1638. DOI:10.1016/j.celrep.2015.02.012 · 8.36 Impact Factor
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