S100A8 inhibits PDGF-induced proliferation of airway smooth muscle cells dependent on the receptor for advanced glycation end-products

BACKGROUND: Airway remodeling is a key feature of asthma, characterized by increased proliferation of airway smooth muscle cells (ASMCs). S100A8 is a calcium-binding protein with a potential to regulate cell proliferation. Here, the effect of exogenous S100A8 protein on the proliferation of ASMCs induced by platelet-derived growth factor (PDGF) and the underlying molecular mechanism was investigated. METHODS: Rat ASMCs were cultured with or without a neutralizing antibody to the receptor for advanced glycation end-products (RAGE), a potential receptor for S100A8 protein. Purified recombinant rat S100A8 protein was then added into the cultured cells, and the proliferation of ASMCs induced by PDGF was detected by colorimetric-based WST-8 assay and ampedance-based xCELLigence proliferation assay. The expression levels of RAGE in ASMCs were analyzed using western blotting assay. RESULTS: Results showed that exogenous S100A8 inhibited the PDGF-induced proliferation of rat ASMCs in a dose- dependent manner with the maximal effect at 1 µg/ml in vitro. Furthermore, when ASMCs was pre-treated with anti-RAGE neutralizing antibody, the inhibitory effect of S100A8 on PDGF-induced proliferation was significantly suppressed. In addition, neither the treatment with S100A8 or PDGF alone nor the pre-treatment with rS100A8 followed by PDGF stimulation affected the expression levels of RAGE. CONCLUSIONS: Our study demonstrated that S100A8 inhibits PDGF-induced ASMCs proliferation in a manner dependent on membrane receptor RAGE.

Study on the mechanism of S100A9-induced secretion of vascular endothelial growth factor-A by monocytes / 国际检验医学杂志

Objective To explore the molecular mechanism of S100A9-induced secretion of vascular endothelial growth factor-A (VEGF-A)by monocytes.Methods Peripheral blood specimen were collected from healthy individuals undergoing physical exami-nation and the CD14 + monocytes were purified by using immunomagnetic beads and the expression of the receptor for advanced gly-cation endproducts (RAGE)was detected by flow cytomertry.In vitro CD14 + monocytes were stimulated by S100A9,and anti-RAGE antibody or NK-κB signal pathway inhibitor were pre-incubated for 1 hour and then stimulated by S100A9,the levels of VEGF-A were detected by using enzyme-linked immunosorbent assay.Results The high level of RAGE was expressed by isolated CD14 + monocytes,after S100A9 stimulation,the secretion of VEGF-A by CD14 + monocytes was significantly increased in a dose and time dependent manner.However,the inducing VEGF-A was significantly decreased(P <0.01 ),while pre-treated with anti-RAGE antibody or NK-κB inhibitor (P <0.01).Conclusion S100A9 inducing the secretion of VEGF-A by monocytes and is de-pended on RAGE-NK-κB signal pathway,suggesting that S100A9 might promote angiogenesis.