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

Lamacchia, Céline; Rodriguez, Emiliana; Palmer-Lourenco, Gaby; Gabay, Cem

doi:10.1016/j.cyto.2013.04.010

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Title		Endogenous IL-1α is a chromatin-associated protein in mouse macrophages
Authors		Lamacchia, Céline Rodriguez, Emiliana Palmer-Lourenco, Gaby Gabay, Cem
Published in		Cytokine. 2013, vol. 63, no. 2, p. 135-44
Abstract		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.
Keywords		Animals — Cell Line — Cell Nucleus — Chromatin/metabolism — Humans — Immunity, Innate — Inflammasomes/immunology/metabolism — Interleukin-1alpha/deficiency/genetics/metabolism — Interleukin-1beta/biosynthesis/metabolism — Lipopolysaccharides — Macrophage Activation — Macrophages/immunology/metabolism — Mice — Mice, Inbred C57BL — Mice, Knockout
Identifiers		DOI: 10.1016/j.cyto.2013.04.010 PMID: 23684408
Full text		Article (Published version) (1.3 MB) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
Research group		Mécanisme de l'inflammation articulaire (44)
Citation (ISO format)		LAMACCHIA, Céline et al. Endogenous IL-1α is a chromatin-associated protein in mouse macrophages. In: Cytokine, 2013, vol. 63, n° 2, p. 135-44. doi: 10.1016/j.cyto.2013.04.010 https://archive-ouverte.unige.ch/unige:46005