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Antioxid Redox Signal. 2015 Dec 10;23(17):1305-15. doi: 10.1089/ars.2015.6383. Epub 2015 Jul 27.

Therapeutic Opportunities in Damage-Associated Molecular Pattern-Driven Metabolic Diseases.

Author information

1
1 Section of Digestive Diseases, Department of Internal Medicine, Yale University , New Haven, Connecticut.
2
2 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University , Mansoura, Egypt .

Abstract

SIGNIFICANCE:

Sterile inflammation is a common finding present in various metabolic disorders. This type of inflammation is mediated by damage-associated molecular patterns (DAMPs) that are released upon cellular injury to activate pattern recognition receptors on innate immune cells and amplify organ damage.

RECENT ADVANCES:

In the last decade, DAMPs, such as high-mobility group protein B1, nucleic acids (DNA, RNA), adenosine triphosphate, and other metabolites, were found to contribute to the inflammatory response in diabetes, gout, obesity, steatohepatitis, and atherosclerosis. Varied receptors, including Toll-like receptors (TLRs), the purinergic P2X(7) receptors, and nucleotide-binding domain, and leucine-rich repeat protein 3 (NLRP3)-inflammasome sense DAMPs and DAMP-like molecules and release the proinflammatory cytokines, interleukin (IL)-1β and IL-18.

CRITICAL ISSUES:

Available therapeutic approaches that interfered with the signaling of TLRs, P2X(7), NLRP3-inflammasome, and IL-1β showed encouraging results in metabolic diseases, which will be also highlighted in this review.

FUTURE DIRECTIONS:

It is important to understand the origination of DAMPs and how they contribute to the inflammatory response in metabolic disorders to develop selective and efficient therapeutics for intervention.

PMID:
26055926
PMCID:
PMC4685500
DOI:
10.1089/ars.2015.6383
[Indexed for MEDLINE]
Free PMC Article

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