Ninjurin1 regulates lipopolysaccharide-induced inflammation through direct binding

作者：Shin Min Wook; Bae Sung Jin; Wee Hee Jun; Lee Hyo Jong; Ahn Bum Ju; Le Hoang; Lee Eun Ji; Kim Ran Hee; Lee Hye Shin; Seo Ji Hae; Park Ji Hyeon; Kim Kyu Won^*

来源：International Journal of Oncology, 2016, 48(2): 821-828.

DOI：10.3892/ijo.2015.3296

• ninjurin1
• lipopolysaccharide
• lipopolysaccharide binding
• inflammation
• macrophage

Ninjurin1 is a transmembrane protein involved in macrophage migration and adhesion during inflammation. It was recently reported that repression of Ninjurin1 attenuated the lipopolysaccharide (LPS)-induced inflammatory response in macrophages; however, the precise mechanism by which Ninjurin1 modulates LPS-induced inflammation remains poorly understood. In the present study, we found that the interaction between Ninjurin1 and LPS contributed to the LPS-induced inflammatory response. Notably, pull-down assays using lysates from HEK293T cells transfected with human or mouse Ninjurin1 and biotinylated LPS (LPS-biotin) showed that LPS directly bound Ninjurin1. Subsequently, LPS binding assays with various truncated forms of Ninjurin1 protein revealed that amino acids (aa) 81-100 of Ninjurin1 were required for LPS binding. In addition, knockdown experiments using Ninj1 siRNA resulted in decreased nitric oxide (NO) and tumor necrosis factor-alpha (TNF alpha) secretion upon LPS treatment in Raw264.7 cells. Collectively, our results suggest that Ninjurin1 regulates the LPS-induced inflammatory response through its direct binding to LPS, thus, identifying Ninjurin1 as a putative target for the treatment of inflammatory diseases, such as sepsis and inflammation-associated carcinogenesis.

• 出版日期2016-2