Reverse signaling through BAFF differentially regulates the expression of inflammatory mediators and cytoskeletal movements in THP-1 cells

Sung Tak Jeon, Won Jung Kim, Sang Min Lee, Min Young Lee, Seung Beom Park, Seung Hee Lee, In San Kim, Kyoungho Suk, Beom Kyu Choi, Eun M. Choi, Byoung S. Kwon, Won Ha Lee

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Most members of the tumor-necrosis factor superfamily have been reported to mediate reverse signaling in T cells, macrophages, and/or dendritic cells. BAFF has been reported to have important functions in B-cell survival through forward signaling, but the presence of reverse signaling has not been explored. To investigate the possibility of BAFF-mediated reverse signaling, the expression patterns and functions of BAFF were analyzed in monocytic cell lines including the human macrophage-like cell line, THP-1. The expression of BAFF and its receptors was detected in monocytic cell lines, either before or after activation. The stimulation of BAFF induced the expression of matrix metalloproteinase (MMP)-9, interleukin -8, and transforming growth factor-β-induced gene product (βig-h3) and the upregulation of intercellular adhesion molecule-1 in THP-1 cells. The activation of mitogen-activated protein kinase extracellular signal-regulated kinase1/2 and nuclear factor-κB was required for these responses. In addition to these stimulatory effects, BAFF-mediated signaling inhibited processes involving cytoskeletal movement such as phagocytosis and transmigration through blocking the activation of phosphatidylinositol 3-kinase/AKT and Rac-1. Furthermore, murine primary macrophage culture such as peritoneal macrophages expressed BAFF and stimulation of it induced the expression of MMP-9. These observations show that the reverse signaling initiated from BAFF induces the expression of inflammatory mediators while suppressing the cytoskeletal movements associated with phagocytosis and transmigration.

Original languageEnglish
Pages (from-to)148-156
Number of pages9
JournalImmunology and Cell Biology
Volume88
Issue number2
DOIs
Publication statusPublished - 2010 Feb 1

Keywords

  • Atherosclerosis
  • BAFF
  • Inflammation
  • Macrophage
  • Rheumatoid arthritis
  • Signaling transduction

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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  • Cite this

    Jeon, S. T., Kim, W. J., Lee, S. M., Lee, M. Y., Park, S. B., Lee, S. H., Kim, I. S., Suk, K., Choi, B. K., Choi, E. M., Kwon, B. S., & Lee, W. H. (2010). Reverse signaling through BAFF differentially regulates the expression of inflammatory mediators and cytoskeletal movements in THP-1 cells. Immunology and Cell Biology, 88(2), 148-156. https://doi.org/10.1038/icb.2009.75