Human S100A7 Induces Mature Interleukin1α Expression by RAGE-p38 MAPK-Calpain1 Pathway in Psoriasis.

Abstract

Psoriatic keratinocytes express exaggerated levels of inflammatory cytokines, and show aberrant hyperproliferation and terminal differentiation in the pathogenesis of psoriasis. The antimicrobial protein hS100A7 (psoriasin) has been found highly expressed in psoriatic skin, but the mechanism and physiological function remain largely unknown. We observed that hS100A7 induces mature interleukin 1α (17kDa) expression in normal human epidermal keratinocytes, which is dependent on RAGE-p38 MAPK and calpain-1 as the inhibitors or knockdown of them completely decreased the expression of mature interleukin1α. Then, we proved mS100a7a15, mature IL-1α and calpain-1 were highly expressed in imquimod-induced psoriasis model and mouse IL-17a-neutralizing antibody treatment attenuated mS100a7a15 expression. At last, PD 151746 (calpain-1 inhibitor) treatment decreased epidermal thickness in imquimod-induced psoriasis model. Taken together, our results suggest that mature IL-1α induced by hS100A7 is via RAGE-p38 MAPK and calpain-1 pathway in keratinocyte and this mechanism may play an important role during psoriasis.

• Authors: Hu Lei, Xiangyun Li, Bo Jing, Hanzhang Xu, Yingli Wu
• Journal: PloS one (PLoS One) Vol. 12 Issue 1 Pg. e0169788 ( 2017) ISSN: 1932-6203 [Electronic] United States
• PMID: 28060905 (Publication Type: Journal Article)

Chemical References

• Acrylates
• Interleukin-1alpha
• PD 151746
• Receptor for Advanced Glycation End Products
• S100 Calcium Binding Protein A7
• S100 Proteins
• S100A7 protein, human
• p38 Mitogen-Activated Protein Kinases
• Calpain
• CAPNS1 protein, human

Topics

• Acrylates (pharmacology)
• Animals
• Calpain (metabolism)
• Cell Line
• Disease Models, Animal
• Gene Expression
• Humans
• Hyperplasia
• Interleukin-1alpha (genetics, metabolism)
• Keratinocytes (metabolism)
• Mice
• Proteolysis
• Psoriasis (genetics, metabolism, pathology)
• Receptor for Advanced Glycation End Products (metabolism)
• S100 Calcium Binding Protein A7
• S100 Proteins (metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)