title: Chemotactic activity of S100A7 (Psoriasin) is mediated by the receptor for advanced glycation end products and potentiates inflammation with highly homologous but functionally distinct S100A15.
abstract: Human S100A7 (psoriasin) is overexpressed in inflammatory diseases. The recently discovered, co-evolved hS100A15 is almost identical in sequence and up-regulated with hS100A7 during cutaneous inflammation. The functional role of these closely related proteins for inflammation remains undefined. By generating specific Abs, we demonstrate that hS100A7 and hS100A15 proteins are differentially expressed by specific cell types in the skin. Although highly homologous, both proteins are chemoattractants with distinct chemotactic activity for leukocyte subsets. We define RAGE (receptor for advanced glycation end products) as the hS100A7 receptor, whereas hS100A15 functions through a Gi protein-coupled receptor. hS100A7-RAGE binding, signaling, and chemotaxis are zinc-dependent in vitro, reflecting the previously reported zinc-mediated changes in the hS100A7 dimer structure. When combined, hS100A7 and hS100A15 potentiate inflammation in vivo. Thus, proinflammatory synergism in disease may be driven by the diverse biology of these almost identical proteins that have just recently evolved. The identified S100A7 interaction with RAGE may provide a novel therapeutic target for inflammation.
authors.affiliation: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Wolf
authors.forename: O M Zack
authors.initials: OM
authors.lastname: Howard
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Dong
authors.forename: Christopher
authors.initials: C
authors.lastname: Voscopoulos
authors.forename: Karen
authors.initials: K
authors.lastname: Boeshans
authors.forename: Jason
authors.initials: J
authors.lastname: Winston
authors.forename: Rao
authors.initials: R
authors.lastname: Divi
authors.forename: Michele
authors.initials: M
authors.lastname: Gunsior
authors.forename: Paul
authors.initials: P
authors.lastname: Goldsmith
authors.forename: Bijan
authors.initials: B
authors.lastname: Ahvazi
authors.forename: Triantafyllos
authors.initials: T
authors.lastname: Chavakis
authors.forename: Joost J
authors.initials: JJ
authors.lastname: Oppenheim
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Yuspa
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002634:Chemotaxis, Leukocyte; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016131:Lymphocyte Subsets; D051379:Mice; D018345:Mice, Knockout; D000067759:Receptor for Advanced Glycation End Products; D043562:Receptors, G-Protein-Coupled / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000276:immunology / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; D000067759:Receptor for Advanced Glycation End Products; D043562:Receptors, G-Protein-Coupled; D011971:Receptors, Immunologic; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; C510475:S100A7A protein, human