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Soluble Siglec-9 alleviates intestinal inflammation through inhibition of the NF-κB pathway

Authors
 Eun Ae Kang  ;  Hosim Soh  ;  Seona Park  ;  Hyun Jung Lee  ;  Jong Pil Im  ;  Joo Sung Kim 
Citation
 INTERNATIONAL IMMUNOPHARMACOLOGY, Vol.86 : 106695, 2020-09 
Journal Title
 INTERNATIONAL IMMUNOPHARMACOLOGY 
ISSN
 1567-5769 
Issue Date
2020-09
Keywords
Experimental colitis ; Inflammatory bowel diseases ; NF–κB ; Siglec–9
Abstract
Background: Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a superfamily of immunoreceptors recognizing sialic acid. Siglec-9 has been shown to mediate inhibitory immune responses. The aim of this study was to evaluate the effect of a soluble form of Siglec-9 (sSiglec-9) on inflamed intestinal epithelial cells (IECs), murine macrophages, and experimental murine colitis models. Methods: COLO 205 human IECs and RAW 264.7 murine macrophages were pretreated with sSiglec-9 and then stimulated with TNF-α or lipopolysaccharides, respectively. The expression of proinflammatory cytokines such as IL-8 and TNF-α was measured using real-time RT-PCR and ELISA. To demonstrate the inhibitory effects of sSiglec-9 on the NF-κB pathway, IκBα phosphorylation/degradation was determined using western blotting and the DNA binding activity of NF-κB was evaluated using an electrophoretic mobility shift assay. Further, mouse models with dextran sulfate sodium-induced acute colitis and piroxicam-induced IL-10-/- chronic colitis were generated. Intraperitoneal injections of sSiglec-9 were performed, and body weight, colon length, and histopathologic findings were examined. Results: sSiglec-9 suppressed IL-8 and TNF-α gene expression in stimulated COLO 205 and RAW 264.7 cells. sSiglec-9 inhibited IκBα phosphorylation/degradation and the DNA binding activity of NF-κB. sSiglec-9 injections significantly ameliorated weight loss, colon shortening, and the severity of intestinal inflammation in acute and chronic colitis mouse models. Conclusion: sSiglec-9 may inhibit NF-κB activation in IECs and macrophages and alleviate experimental colitis in mice, suggesting that sSiglec-9 is a potential therapeutic agent for the treatment of inflammatory bowel disease.
Full Text
https://www.sciencedirect.com/science/article/pii/S1567576920310031
DOI
10.1016/j.intimp.2020.106695
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Eun Ae(강은애)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/180010
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