The Journal of biological chemistry, 2002-12, Vol.277 (49), p.47444-47450
2002
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- Autor(en) / Beteiligte
- Titel
- Inhibition of p38 MAPK by Glucocorticoids via Induction of MAPK Phosphatase-1 Enhances Nontypeable Haemophilus influenzae-induced Expression of Toll-like Receptor 2
- Ist Teil von
- The Journal of biological chemistry, 2002-12, Vol.277 (49), p.47444-47450
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2002
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Despite the importance of glucocorticoids in suppressing immune and inflammatory responses, their role in enhancing host immune and defense response against invading bacteria is poorly understood. We have demonstrated recently that glucocorticoids synergistically enhance nontypeable Haemophilus influenzae(NTHi)-induced expression of Toll-like receptor 2 (TLR2), an important TLR family member that has been shown to play a critical role in host immune and defense response. However, the molecular mechanisms underlying the glucocorticoid-mediated enhancement of TLR2 induction still remain unknown. Here we show that glucocorticoids synergistically enhance NTHi-induced TLR2 expression via specific up-regulation of the MAPK phosphatase-1 (MKP-1) that, in turn, leads to dephosphorylation and inactivation of p38 MAPK, the negative regulator for TLR2 expression. Moreover, increased expression of TLR2 in epithelial cells greatly enhances the NTHi-induced expression of several key cytokines, including tumor necrosis factor-α and interleukins 1β and 8, thereby contributing significantly to host immune and defense response. These studies may bring new insights into the novel role of glucocorticoids in orchestrating and optimizing host immune and defense responses during bacterial infections and enhance our understanding of the signaling mechanisms underlying the glucocorticoid-mediated attenuation of MAPKs.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0021-9258eISSN: 1083-351XDOI: 10.1074/jbc.M208140200Titel-ID: cdi_proquest_miscellaneous_72718927
- Format
- –
- Schlagworte
- Blotting, Western, Bronchi - cytology, Cell Cycle Proteins, Cells, Cultured, Dexamethasone - pharmacology, Drosophila Proteins, Dual Specificity Phosphatase 1, Glucocorticoids - metabolism, Haemophilus influenzae - metabolism, HeLa Cells, Humans, Immediate-Early Proteins - metabolism, Interleukin-1 - biosynthesis, Interleukin-1 - metabolism, Interleukin-8 - biosynthesis, Interleukin-8 - metabolism, MAP Kinase Signaling System, Membrane Glycoproteins - metabolism, Mitogen-Activated Protein Kinases - antagonists & inhibitors, Mitogen-Activated Protein Kinases - metabolism, Models, Biological, p38 Mitogen-Activated Protein Kinases, Phosphoprotein Phosphatases, Phosphorylation, Plasmids - metabolism, Protein Binding, Protein Biosynthesis, Protein Phosphatase 1, Protein Synthesis Inhibitors - pharmacology, Protein Tyrosine Phosphatases - metabolism, Receptors, Cell Surface - metabolism, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Time Factors, Toll-Like Receptor 2, Toll-Like Receptors, Transfection, Tumor Necrosis Factor-alpha - metabolism, Up-Regulation