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.
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.
Wolf
Ronald
R
Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Howard
O M Zack
OM
Dong
Hui-Fang
HF
Voscopoulos
Christopher
C
Boeshans
Karen
K
Winston
Jason
J
Divi
Rao
R
Gunsior
Michele
M
Goldsmith
Paul
P
Ahvazi
Bijan
B
Chavakis
Triantafyllos
T
Oppenheim
Joost J
JJ
Yuspa
Stuart H
SH
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*
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