title: IL-1α and IL-1β recruit different myeloid cells and promote different stages of sterile inflammation.
abstract: The immune system has evolved to protect the host from invading pathogens and to maintain tissue homeostasis. Although the inflammatory process involving pathogens is well documented, the intrinsic compounds that initiate sterile inflammation and how its progression is mediated are still not clear. Because tissue injury is usually associated with ischemia and the accompanied hypoxia, the microenvironment of various pathologies involves anaerobic metabolites and products of necrotic cells. In the current study, we assessed in a comparative manner the role of IL-1α and IL-1β in the initiation and propagation of sterile inflammation induced by products of hypoxic cells. We found that following hypoxia, the precursor form of IL-1α, and not IL-1β, is upregulated and subsequently released from dying cells. Using an inflammation-monitoring system consisting of Matrigel mixed with supernatants of hypoxic cells, we noted accumulation of IL-1α in the initial phase, which correlated with the infiltration of neutrophils, and the expression of IL-1β correlated with later migration of macrophages. In addition, we were able to show that IL-1 molecules from cells transfected with either precursor IL-1α or mature IL-1β can recruit neutrophils or macrophages, respectively. Taken together, these data suggest that IL-1α, released from dying cells, initiates sterile inflammation by inducing recruitment of neutrophils, whereas IL-1β promotes the recruitment and retention of macrophages. Overall, our data provide new insight into the biology of IL-1 molecules as well as on the regulation of sterile inflammation.
authors.affiliation: The Shraga Segal Department of Microbiology and Immunology and The Cancer Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel.
authors.forename: Peleg
authors.initials: P
authors.lastname: Rider
authors.forename: Yaron
authors.initials: Y
authors.lastname: Carmi
authors.forename: Ofer
authors.initials: O
authors.lastname: Guttman
authors.forename: Alex
authors.initials: A
authors.lastname: Braiman
authors.forename: Idan
authors.initials: I
authors.lastname: Cohen
authors.forename: Elena
authors.initials: E
authors.lastname: Voronov
authors.forename: Malka R
authors.initials: MR
authors.lastname: White
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
authors.forename: Ron N
authors.initials: RN
authors.lastname: Apte
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology*; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000145:classification / Q000276:immunology / Q000473:pathology; D018836:Inflammation Mediators / Q000145:classification / Q000502:physiology*; D053582:Interleukin-1alpha / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D053583:Interleukin-1beta / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: C508584:IL1A protein, human; C508585:IL1B protein, human; D018836:Inflammation Mediators; D053582:Interleukin-1alpha; D053583:Interleukin-1beta