Alarmins: Feel the stress

Peleg Rider, Elena Voronov, Charles A. Dinarello, Ron N. Apte, Idan Cohen

Research output: Contribution to journalReview articlepeer-review

143 Scopus citations

Abstract

Over the last decade, danger-associated molecular pattern molecules, or alarmins, have been recognized as signaling mediators of sterile inflammatory responses after trauma and injury. In contrast with the accepted passive release models suggested by the "danger hypothesis," it was recently shown that alarmins can also directly sense and report damage by signaling to the environment when released from live cells undergoing physiological stress, even without loss of subcellular compartmentalization. In this article, we review the involvement of alarmins such as IL-1α, IL-33, IL-16, and high-mobility group box 1 in cellular and physiological stress, and suggest a novel activity of these molecules as central initiators of sterile inflammation in response to nonlethal stress, a function we denote "stressorins." We highlight the role of posttranslational modifications of stressorins as key regulators of their activity and propose that targeted inhibition of stressorins or their modifiers could serve as attractive new anti-inflammatory treatments for a broad range of diseases.

Original languageEnglish
Pages (from-to)1395-1402
Number of pages8
JournalJournal of Immunology
Volume198
Issue number4
DOIs
StatePublished - 15 Feb 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
Copyright © 2017 by The American Association of Immunologists, Inc.

Funding

This work was supported by the Ministry of Aliya and Immigrant Asorption (I.C.); the Center for Absorption in Science, Israel (I.C.); the Israel Ministry of Science jointly with the Deutsches Krebsforschungscentrum, Heidelberg, Germany (R.N.A. and E.V.); the Israel Science Foundation supported by the Israel Academy of Sciences and Humanities (R.N.A. and E.V.); the Israel Cancer Association and the Israel Ministry of Health Chief Scientist's Office, 7th Framework Programme for Research and Technological Development: Cancer Inflammation (INFLA-CARE) (R.N.A. and E.V.); the Binational (Israel) Science Foundation (R.N.A. and E.V.); and the German-Israeli Foundation (R.N.A. and E.V.)

FundersFunder number
7th Framework Programme for Research and Technological Development: Cancer Inflammation
Center for Absorption in Science, Israel
INFLA-CARE
Israel Ministry of Science
Ministry of Aliya and Immigrant Asorption
German Cancer Research Center
German-Israeli Foundation for Scientific Research and Development
United States-Israel Binational Science Foundation
Israel Academy of Sciences and Humanities
Israel Cancer Association
Israel Science Foundation
Office of the Chief Scientist, Ministry of Health

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