Your browser doesn't support javascript.
loading
Crosstalk between signals initiated from TLR4 and cell surface BAFF results in synergistic induction of proinflammatory mediators in THP-1 cells.
Lim, Su-Geun; Kim, Jae-Kwan; Suk, Kyoungho; Lee, Won-Ha.
Afiliação
  • Lim SG; School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Republic of Korea.
  • Kim JK; School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Republic of Korea.
  • Suk K; Department of Pharmacology, Brain Science &Engineering Institute, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu 41944, Republic of Korea.
  • Lee WH; School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Republic of Korea.
Sci Rep ; 7: 45826, 2017 04 04.
Article em En | MEDLINE | ID: mdl-28374824
ABSTRACT
Cellular response to stimulation is mediated by meshwork of signaling pathways that may share common signaling adaptors. Here, we present data demonstrating that signaling pathways initiated from the membrane-bound form of B-cell activating factor (BAFF) can crosstalk with lipopolysaccharide (LPS)-induced signaling for synergistic expression of proinflammatory mediators in the human macrophage-like cell line THP-1. Co-treatment of the cells with BAFF-specific monoclonal antibody and LPS resulted in enhanced mitogen-activated protein kinase (MAPK)/mitogen- and stress-activated protein kinase (MSK)-mediated phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 subunit (Ser276), which then interacts with CREB binding protein (CBP) for subsequent acetylation. Simultaneously, the phosphorylation of cyclic AMP-response element binding protein (CREB) was enhanced through the combined action of phosphatidylinositol-3-kinase (PI3K)/AKT and MAPK/MSK pathways, and the resulting phospho-CREB interacted with the NF-κB/CBP complex. Transfection of CREB-specific siRNA inhibited the BAFF-mediated enhancing effect indicating that the formation of the CREB/NF-κB/CBP complex is required for the synergistic induction of the proinflammatory genes. These findings indicate that BAFF-mediated reverse signaling can modulate LPS-induced inflammatory activation through regulation of NF-κB and CREB activity and point out the necessity to re-evaluate the role of BAFF in diseases where its expression is high in macrophages.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Adaptadoras de Transdução de Sinal / Receptor 4 Toll-Like / Fator Ativador de Células B / Inflamação / Proteínas de Membrana Limite: Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Adaptadoras de Transdução de Sinal / Receptor 4 Toll-Like / Fator Ativador de Células B / Inflamação / Proteínas de Membrana Limite: Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article