title: BAFF and APRIL induce inflammatory activation of THP-1 cells through interaction with their conventional receptors and activation of MAPK and NF-κB.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Life Sciences and Biotechnology, Kyungpook National University, Daegu, 702-701, Korea.
authors.forename: Sang-Min
authors.initials: SM
authors.lastname: Lee
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Kim
authors.forename: Kyoungho
authors.initials: K
authors.lastname: Suk
authors.forename: Won-Ha
authors.initials: WH
authors.lastname: Lee
mesh_terms: D053264:B-Cell Activating Factor / Q000276:immunology* / Q000378:metabolism; D053265:B-Cell Activation Factor Receptor / Q000378:metabolism; D053301:B-Cell Maturation Antigen / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D007249:Inflammation / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction; D053303:Transmembrane Activator and CAML Interactor Protein / Q000378:metabolism; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000276:immunology* / Q000378:metabolism
chemical_list: D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; D016209:Interleukin-8; D016328:NF-kappa B; C086966:TNFRSF17 protein, human; C114631:TNFSF13 protein, human; C505719:TNFSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D020928:Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9