BAFF and APRIL induce inflammatory activation of THP-1 cells through interaction with their conventional receptors and activation of MAPK and NF-κB
- 345 Downloads
BAFF and APRIL, as closely related members of the TNF superfamily, are important regulators of B-cell survival. They share two receptors, TACI and BCMA, and BAFF can stimulate an additional receptor, BAFF-R. Although these molecules have been under intense investigation in order to identify their role in immune reactions, the effect of BAFF and APRIL on macrophage function has not been tested.
The human macrophage-like cell line THP-1, which expresses BAFF/APRIL and all three of their receptors, was stimulated with recombinant human BAFF or APRIL or monoclonal antibodies against the receptors and the resulting cellular responses were investigated. Treatment of the cells with these agents induced the expression of pro-inflammatory mediators such as matrix metalloproteinase (MMP)-9 and IL-8. Suppression of the expression of these receptors using specific siRNAs resulted in the blocking of the response, confirming that these responses require specific interaction between BAFF/APRIL and their receptors. Inhibitors of MAPK and NF-κB blocked the expression of IL-8. Furthermore, inhibitors of MAPK blocked the BAFF-induced specific DNA binding activity of NF-κB.
These data indicate that BAFF and APRIL can induce inflammatory activation of THP-1 cells through the activation of MAPK, which leads to the subsequent activation of NF-κB.
KeywordsBAFF APRIL MAPK NF-κB Inflammation
This work was supported by a grant provided by the Korean Ministry of Education, Science and Technology (The Regional Core Research Program/Anti-aging and Well-being Research Center).
- 15.Xi H, Katschke KJ Jr, Helmy KY, Wark PA, Kljavin N, Clark H, et al. Negative regulation of autoimmune demyelination by the inhibitory receptor CLM-1. J Exp Med. 2010;207(7–16):S1–5.Google Scholar
- 19.Kim WJ, Lee WH. LIGHT is expressed in foam cells and involved in destabilization of atherosclerotic plaques through induction of matrix metalloproteinase-9 and IL-8. Immune Netw. 2004;4:116–22.Google Scholar
- 20.Merighi S, Benini A, Mirandola P, Gessi S, Varani K, Leung E, et al. A3 adenosine receptor activation inhibits cell proliferation via phosphatidylinositol 3-kinase/Akt-dependent inhibition of the extracellular signal-regulated kinase 1/2 phosphorylation in A375 human melanoma cells. J Biol Chem. 2005;280:19516–26.PubMedCrossRefGoogle Scholar