Nucleolin Mediates LPS-induced Expression of Inflammatory Mediators and Activation of Signaling Pathways
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Current Medical Science 40(4):646-653,2020 Current Medical Science 40(4):2020 DOI https://doi.org/10.1007/s11596-020-2229-6
Nucleolin Mediates LPS-induced Expression of Inflammatory Mediators and Activation of Signaling Pathways* Li FANG1#, Kang-kai WANG2, Qing HUANG1, Feng CHENG1, Fang HUANG1, Wei-wei LIU1 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 The Author(s) 2020
Summary: In this study, we investigated the effects of nucleolin on lipopolysaccharide (LPS)induced activation of MAPK and NF-KappaB (NF-κB) signaling pathways and secretion of TNF-α, IL-1β and HMGB1 in THP-1 monocytes. Immunofluorescence assay and Western blotting were used to identify the nucleolin expression in cell membrane, cytoplasm and nucleus of THP1 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-α, IL1β and HMGB1) and activation of MAPK and NF-κB/I-κB 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-α, IL-1β and HMGB1. P38, JNK, ERK and NF-κB subunit p65 inhibitors could significantly inhibit the secretion of IL-1β, TNF-α 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-α and IL-1β 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-α, IL-1β and HMGB1). Key words: nucleolin; THP-1 monocytes; lipopolysaccharide; MAPK; NF-κB signaling pathway; inflammatory mediators
As a type of phosphoric acid protein in eukaryotic cells, nucleolin (rRNA) is mainly involved in the ribosomal transcription, ribosome subunit assembly, maturation and so on[1–4]. In most cells, nucleolin is mainly expressed in the nucleus, but it can also exist in the cytoplasm in glycosylated or phosphorylated form. Recent studies have found that nucleolin is expressed on the surface of a variety of immune cells, tumor cells and vascular endothelial cells, it acts as receptors for many proteins, viruses and bacteria or co-receptors, and it is involved in the pathogenic microbial infection, inflammation, angiogenes
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