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Cell‐surface nucleolin is involved in lipopolysaccharide internalization and signalling in alveolar macrophages
Author(s) -
Wang Yi,
Mao Mei,
Xu Jiancheng
Publication year - 2011
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1042/cbi20100625
Subject(s) - nucleolin , internalization , cytoplasm , microbiology and biotechnology , lipopolysaccharide , cell , tumor necrosis factor alpha , gene knockdown , chemistry , small interfering rna , receptor , biology , immunology , apoptosis , rna , biochemistry , gene , nucleolus
C23 (nucleolin) shuttling between the nucleus, cytoplasm and cell surface has been implicated in controlling regulatory processes and may play a role in pathogen infection and autoimmune diseases. It has been reported that cell surface‐expressed C23 on THP‐1 monocytes is involved in the inflammatory response induced by LPS (lipopolysaccharide). This study investigates whether C23 is a membrane receptor for LPS during LPS‐induced AMs (alveolar macrophages) activation. First, using immunofluorescence and microscopy, we detected the expression of C23 on the surface of AMs. Second, using LPS affinity columns, we demonstrated that C23 directly binds to LPS. Third, we found that LPS colocalized with C23 on both the cell surface and in the cytoplasm. Finally, knockdown of C23 expression on the cell surface using siRNA (small interfering RNA) led to significant reductions in the internalization of LPS, in LPS‐induced NF‐κB (nuclear factor κB)–DNA binding and in the protein expression of TNF (tumour necrosis factor)‐α and IL‐6 (interleukin‐6). These findings provide evidence that cell‐surface C23 on AMs may serve as a receptor for LPS and are essential for internalization and transport of LPS. Furthermore, C23 participates in the regulation of LPS‐induced inflammation of AMs, which indicates that cell‐surface C23 is a new and promising therapeutic target for the treatment of bacterial infections.