Nucleolin Mediates LPS-induced Expression of Inflammatory Mediators and Activation of Signaling Pathways  

作　　者：Li FANG Kang-kai WANG Qing HUANG Feng CHENG Fang HUANG Wei-wei LIU 

机构地区：[1]Department of Cardiology,the First Hospital of Changsha,Changsha 410008,China [2]Department of Pathophysiology,Xiangya School of Medicine,Central South University,Changsha 410008,China

出　　处：《Current Medical Science》2020年第4期646-653,共8页当代医学科学（英文）

基　　金：This work was supported by grants from Bureau of Science and Technology of Changsha,China(No.Kq 1701007);Hunan Natural Science Foundation,China(No.2018JJ6127).

摘　　要：Summary:In this study,we investigated the effects of nucleolin on lipopolysaccharide(LPS)-induced activation of MAPK and NF-KappaB(NF-kB)signaling pathways and secretion of TNF-a,IL-1βand HMGB1 in THP-1 monocytes.Immunofluorescence assay and Western blotting were used to identify the nucleolin expression in cell membrane,cytoplasm and nucleus of THP-1 monocytes.Inactivation of nucleolin was induced by neutralizing antibody against nucleolin.THP-1 monocytes were pretreated with anti-nucleolin antibody for 1 h prior to LPS challenge.The irrelevant IgG group was used as control.Secretion of inflammatory mediators(TNF-a,IL-1β and HMGB1)and activation of MAPK and NF-kB/I-kB signaling pathways were examined to assess the effects of nucleolin on LPS-mediated inflammatory response.Nucleolin existed in cell membrane,cytoplasm and nucleus of THP-1 monocytes.Pretreatment of anti-nucleolin antibody significantly inhibited the LPS-induced secretion of TNF-a,IL-1β and HMGB1.P38,JNK,ERK and NF-κB subunit p65 inhibitors could significantly inhibit the secretion of IL-1β,TNF-a and HMGB1 induced by LPS.Moreover,the phosphorylation of p38,JNK,ERK and p65(or nuclear translocation of p65)was significantly increased after LPS challenge.In contrast,pretreatment of anti-nucleolin antibody could significantly inhibit the LPS-induced phosphorylation of p38,JNK,ERK and p65(or nuclear translocation of p65).However,the irrelevant IgG,as a negative control,had no effect on LPS-induced secretion of TNF-a and IL-Iβ and phosphorylation of p38,JNK,ERK and p65(or nuclear translocation of p65).We demonstrated that nucleolin mediated the LPS-induced activation of MAPK and NF-κB signaling pathways,and regulated the secretion of inflammatory mediators(TNF-a,IL-1β and HMGB1).

关 键 词：NUCLEOLIN THP-1 monocytes LIPOPOLYSACCHARIDE MAPK NF-κB signaling pathway inflammatory mediators 

分 类 号：R73[医药卫生—肿瘤]