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Reverse signaling initiated from GITRL induces NF-kappaB activation through ERK in the inflammatory activation of macrophages.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Bae, Eun Mi Kim, Won-Jung Suk, Kyoungho Kang, Young-Mo Park, J. S. Kim, Won Young Choi, Eun Mi Choi, Beom Kyu Kwon, Byoung S. Lee, W. H. |
| Copyright Year | 2008 |
| Abstract | Glucocorticoid-induced TNF receptor family related protein ligand (GITRL) is known to interact with its cognate receptor GITR. In order to investigate the potential role of GITRL in the pro-inflammatory activation of macrophages and the signaling pathway induced by GITRL, we stimulated the macrophage cell line, THP-1, and primary macrophages with an anti-GITRL monoclonal antibody or a GITR:Fc fusion protein and analyzed the cellular responses. The stimulation of GITRL induced the expression of pro-inflammatory cytokines and matrix metalloproteinase (MMP)-9 and up-regulated ICAM-1 expression levels, which was responsible for enhanced cellular aggregation and adhesion to extracellular matrix proteins. The activation of these pro-inflammatory mediators required the activation of ERK1/2 mitogen-activated protein kinase (MAPK) and negatively regulated by p38 MAPK and JNK. Immunofluorescence analysis detected nuclear translocation of the NF-kappaB p50 subunit and this was blocked by ERK inhibitor, indicating that GITRL stimulation induced ERK1/2 phosphorylation and subsequent activation of NF-kappaB. Furthermore, the expression of GITRL and GITR was detected in macrophages in inflammatory disease specimens such as atherosclerotic plaques and synovial tissues of rheumatoid arthritis. These observations raise the possibility that the GITRL-mediated inflammatory activation of macrophages is involved in the pathogenesis of inflammatory diseases. |
| Starting Page | 772 |
| Ending Page | 775 |
| Page Count | 4 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://webbuild.knu.ac.kr/~immunol/articles/2008-Mol%20Imm-%20GITRL%20reverse%20signaling.pdf |
| PubMed reference number | 17602748v1 |
| Volume Number | 45 |
| Issue Number | 2 |
| Journal | Molecular immunology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Atherosclerosis Body tissue Extracellular Matrix Proteins Ligands Matrix Metalloproteinases Metalloproteases Mitogen-Activated Protein Kinases Mitogens Monoclonal Antibodies NF-kappa B Nuclear Translocation Pelvic Inflammatory Disease Rheumatoid Arthritis Senile Plaques Signal Transduction Pathways Specimen TNFRSF18 wt Allele Tumor Necrosis Factor Receptor chimeric protein stress-activated protein kinase 1 |
| Content Type | Text |
| Resource Type | Article |
