title: Recombinant bovine S100A8 and A9 enhance IL-1β secretion of interferon-gamma primed monocytes.
abstract: Calgranulin A (S100A8) and B (S100A9) are found at high levels in inflamed tissue and have been associated with acute and chronic inflammatory disorders. Calgranulins are discussed as damage-associated molecular patterns (DAMPs). To analyze the role of calgranulins for inflammatory responses, bovine S100A8 and S100A9 were cloned, successfully expressed and FPLC-purified. Both molecules did not induce NF-κB activation in boTLR4-transfected HEK293 cells and stimulation of bovine monocytes with both proteins did not result in interleukin 1β (IL-1β) secretion or an upregulated mRNA expression of selected genes (IL1B, TNF, CXCL8, IL10, IL12). However, Interferon γ (IFN-γ) primed bovine monocytes released significantly higher amounts of IL-1β after stimulation with S100A8, S100A9, and co-stimulation with adenosine triphosphate (ATP). In IL-4/IL-13-primed monocytes, the IL-1β release was completely abrogated. The results imply that TLR4/MyD88/NF-κB-independent S100A8/A9-mediated activation of the inflammasome in cattle is favored in a Th1 environment and that S100A8 and S100A9 act as a DAMP in cattle.
authors.affiliation: Immunology Unit, University of Veterinary Medicine Hannover, Bischofsholer Damm 15, D-30173 Hannover, Germany.
authors.forename: Mirja
authors.initials: M
authors.lastname: Koy
authors.forename: Nina
authors.initials: N
authors.lastname: Hambruch
authors.forename: Jamal
authors.initials: J
authors.lastname: Hussen
authors.forename: Christiane
authors.initials: C
authors.lastname: Pfarrer
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Seyfert
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Schuberth
mesh_terms: D000818:Animals; D040501:Calgranulin A / Q000502:physiology*; D040502:Calgranulin B / Q000502:physiology*; D002417:Cattle; D057809:HEK293 Cells; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000502:physiology
chemical_list: D040501:Calgranulin A; D040502:Calgranulin B; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D051197:Toll-Like Receptor 4; D007371:Interferon-gamma
keywords: Cattle; DAMP; Inflammasome; S100