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Endogenous IL-1α is a chromatin-associated protein in mouse macrophages.
Journal article

Endogenous IL-1α is a chromatin-associated protein in mouse macrophages.

  • Lamacchia C Division of Rheumatology, Department of Internal Medicine, University Hospital of Geneva, 26 Avenue Beau-Séjour, 1211 Geneva 14, Switzerland. celinelammacchia@hotmail.com
  • Rodriguez E
  • Palmer G
  • Gabay C
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  • 2013-05-21
Published in:
  • Cytokine. - 2013
Animals
Cell Line
Cell Nucleus
Chromatin
Humans
Immunity, Innate
Inflammasomes
Interleukin-1alpha
Interleukin-1beta
Lipopolysaccharides
Macrophage Activation
Macrophages
Mice
Mice, Inbred C57BL
Mice, Knockout
English The cytokine interleukin-1α (IL-1α) is synthesized as a 31kDa peptide that lacks a leader peptide and is not secreted by the conventional secretory pathway. A distinctive characteristic of pro-IL-1α is the presence of a nuclear localization sequence in its amino-terminal moiety that allows its translocation to the nucleus. However no nuclear function(s) of the endogenous pro-IL-1α has been reported to date. In the present study, we used murine macrophages that produce IL-1α in response to pro-inflammatory stimuli, to gain further insight into the biology of the endogenous IL-1α protein in innate immune cells. We show that endogenous IL-1α is essentially found as a chromatin-associated nuclear protein in LPS-stimulated macrophages. In contrast to IL-1β, IL-1α was not released upon inflammasome activation unless significant cell damage occurred. IL-1β mRNA and protein levels were specifically decreased in IL-1α deficient macrophages after LPS stimulation. However, overexpression of human pro-IL-1α did not rescue this defective IL-1β production, suggesting that this finding might be related to the insertion of the targeting construct into the IL-1 locus, rather than to a specific nuclear function of pro-IL-1α. Finally, by using both genomic and proteomic approaches, we could not identify a nuclear function of IL-1α. Taken together, these observations suggest that in macrophages IL-1α primarily acts as an alarmin that is rapidly released upon cell damage to activate early mechanisms of host defense.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/21237
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