A TLR4-interacting SPA4 peptide inhibits LPS-induced lung inflammation:

Innate Immunity

VijayRamani¹ 

关键词: Inflammation;    surfactant protein-A;    Toll-like receptor-4;    host defense;    protein–protein interaction;   

DOI  :  10.1177/1753425912474851

学科分类：生物科学（综合）

来源: Sage Journals

【 摘 要 】

The interaction between surfactant protein-A (SP-A) and TLR4 is important for host defense. We have recently identified an SPA4 peptide region from the interface of SP-A–TLR4 complex. Here, we studied the involvement of the SPA4 peptide region in SP-A–TLR4 interaction using a two-hybrid system, and biological effects of SPA4 peptide in cell systems and a mouse model. HEK293 cells were transfected with plasmid DNAs encoding SP-A or a SP-A-mutant lacking SPA4 peptide region and TLR4. Luciferase activity was measured as the end-point of SP-A–TLR4 interaction. NF-κB activity was also assessed simultaneously. Next, the dendritic cells or mice were challenged with Escherichia coli-derived LPS and treated with SPA4 peptide. Endotoxic shock-like symptoms and inflammatory parameters (TNF-α, NF-κB, leukocyte influx) were assessed. Our results reveal that the SPA4 peptide region contributes to the SP-A–TLR4 interaction and inhibits the LPS-induced NF-κB activity and TNF-α. We also observed that the SPA4 peptide inhi...

【 授权许可】

CC BY