靶向夏科-莱登晶体的多肽筛选及其在慢性鼻-鼻窦炎伴鼻息肉中的抗炎功能研究OA

OBJECTIVE To screen a specific peptide targeting galectin-10(Gal-10)protein and Charcot-Leyden crystals(CLCs),and evaluate its inhibitory effects on CLC-induced inflammatory responses and its potential therapeutic value in chronic rhinosinusitis with nasal polyps(CRSwNP).METHODS A peptide microarray was used to screen Gal-10-binding peptides.Binding affinity to Gal-10 protein and CLCs was validated using bio-layer interferometry(BLI)and confocal fluorescence microscopy.The secondary structure of the peptide was characterized by circular dichroism(CD)spectroscopy,and cytotoxicity was assessed by lactate dehydrogenase(LDH)release assay and CCK-8 assay.The regulatory effect of the peptide on CLC-induced inflammatory responses was further examined in patient-derived human nasal epithelial cells(HNEpCs)from CRSwNP patients.RESULTS A Gal-10-targeting peptide,4G8R,was identified with a nanomolar binding affinity to Gal-10 protein(KD=4.35±0.14×10-9 M)and selective binding to CLCs.CD spectroscopy revealed a predominantly disordered conformation,and no obvious cytotoxicity was observed in HNEpCs at concentrations ranging from 0.3 to 100 μM.In CRSwNP patients-derived HNEpCs,4G8R significantly downregulated the mRNA expression of IL-1β,IL-6,tumor necrosis factor-α induced by CLCs,with a non-significant downward trend observed for IL-8,and GM-CSF.CONCLUSION Peptide 4G8R selectively binds to CLCs with high affinity and effectively inhibits CLC-induced inflammation responses,representing a novel therapeutic strategy and a promising lead candidate for the targeted treatment of CRSwNP.