title: Ninjurin1 regulates lipopolysaccharide-induced inflammation through direct binding.
abstract: 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-α (TNFα) 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.
authors.affiliation: SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Min Wook
authors.initials: MW
authors.lastname: Shin
authors.affiliation: SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Sung-Jin
authors.initials: SJ
authors.lastname: Bae
authors.affiliation: SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Hee-Jun
authors.initials: HJ
authors.lastname: Wee
authors.affiliation: College of Pharmacy, Inje University, Gimhae, Gyugnam 621-749, Republic of Korea.
authors.forename: Hyo-Jong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Bum Ju
authors.initials: BJ
authors.lastname: Ahn
authors.affiliation: SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Hoang
authors.initials: H
authors.lastname: Le
authors.affiliation: SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Ran Hee
authors.initials: RH
authors.lastname: Kim
authors.affiliation: SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Hye Shin
authors.initials: HS
authors.lastname: Lee
authors.affiliation: SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Ji Hae
authors.initials: JH
authors.lastname: Seo
authors.affiliation: SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Ji-Hyeon
authors.initials: JH
authors.lastname: Park
authors.affiliation: SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Kyu-Won
authors.initials: KW
authors.lastname: Kim
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D009414:Nerve Growth Factors / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000596:Amino Acids; D015816:Cell Adhesion Molecules, Neuronal; D008070:Lipopolysaccharides; D009414:Nerve Growth Factors; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide