Alarmins: Feel the Stress.
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.
Department of Clinical Biochemistry and Pharmacology, Ben Gurion University of the Negev, 84105 Beer-Sheva, Israel.
Peleg
0000-0003-3265-946X
P
Rider
The Shraga Segal Department of Microbiology, Immunology and Genetics, Ben Gurion University of the Negev, 84105 Beer-Sheva, Israel.
Elena
E
Voronov
University of Colorado Denver, Aurora, CO 80045; and.
Charles A
CA
Dinarello
The Shraga Segal Department of Microbiology, Immunology and Genetics, Ben Gurion University of the Negev, 84105 Beer-Sheva, Israel.
Ron N
RN
Apte
Faculty of Medicine, Galilee Medical Center, Nahariya Hospital, 22100 Nahariya, Israel IdanC@gmc.gov.il idan5161@gmail.com.
Idan
I
Cohen
D000067531:Alarmins / Q000502:physiology*; D000818:Animals; D024243:HMGB1 Protein / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D019410:Interleukin-16 / Q000378:metabolism; D053582:Interleukin-1alpha / Q000378:metabolism; D000067596:Interleukin-33 / Q000378:metabolism; D051379:Mice; D011499:Protein Processing, Post-Translational; D013312:Stress, Physiological / Q000276:immunology / Q000502:physiology
D000067531:Alarmins; D024243:HMGB1 Protein; C508584:IL1A protein, human; C506536:IL33 protein, human; D019410:Interleukin-16; D053582:Interleukin-1alpha; D000067596:Interleukin-33