Sterile inflammation: Sensing and reacting to damage

Department of Internal Medicine, Comprehensive Cancer Center, University of Michigan, Michigan 48109, USA.
Nature Reviews Immunology (Impact Factor: 33.84). 11/2010; 10(12):826-37. DOI: 10.1038/nri2873
Source: PubMed

ABSTRACT 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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    • ", 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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    • "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.
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    • "Their numbers increase significantly through recruitment and extravasation in response to chemoattractants secreted locally in response to a wide range of pro-inflammatory sterile and non-sterile stressors. The initiation of inflammation involves the recognition of pathogen-associated molecular patterns (PAMPs) [14] [15] associated with invading microbes or damage-associated molecular patterns (DAMPs) [16]. Macrophages are equipped with a large number of receptors that can recognize PAMPs or DAMPs. "
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