Source:http://linkedlifedata.com/resource/pubmed/id/12356755
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:dateCreated |
2002-11-28
|
| pubmed:abstractText |
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-alpha and interleukins 1beta 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.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DUSP1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone,
http://linkedlifedata.com/resource/pubmed/chemical/Dmel-MKP protein, Drosophila,
http://linkedlifedata.com/resource/pubmed/chemical/Drosophila Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Dual Specificity Phosphatase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Glucocorticoids,
http://linkedlifedata.com/resource/pubmed/chemical/Immediate-Early Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-8,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoprotein Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Phosphatase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Synthesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/TLR2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 2,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
|
| pubmed:status |
MEDLINE
|
| pubmed:author | |
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
47444-50
|
| pubmed:dateRevised |
2009-11-19
|
| pubmed:articleTitle |
Inhibition of p38 MAPK by glucocorticoids via induction of MAPK phosphatase-1 enhances nontypeable Haemophilus influenzae-induced expression of toll-like receptor 2.
|
| pubmed:affiliation |
Gonda Department of Cell and Molecular Biology, House Ear Institute, and the Department of Otolaryngology, University of Southern California, Los Angeles, California 90057, USA.
|