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BMC Mol Biol. 2004 May 4;5:2.

Glucocorticoids synergize with IL-1beta to induce TLR2 expression via MAP Kinase Phosphatase-1-dependent dual Inhibition of MAPK JNK and p38 in epithelial cells.

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Gonda Department of Cell and Molecular Biology, House Ear Institute, and University of Southern California, Los Angeles, CA 90057, USA.



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. Toll-like receptor 2 (TLR2) has recently gained importance as one of the major host defense receptors. The increased expression of TLR2 in response to bacteria-induced cytokines has been thought to be crucial for the accelerated immune response and resensitization of epithelial cells to invading pathogens.


We show that IL-1beta, a key proinflammatory cytokine, greatly up-regulates TLR2 expression in human epithelial cells via a positive IKKbeta-IkappaBalpha-dependent NF-kappaB pathway and negative MEKK1-MKK4/7-JNK1/2 and MKK3/6-p38 alpha/beta pathways. Glucocorticoids synergistically enhance IL-1beta-induced TLR2 expression via specific up-regulation of the MAP kinase phosphatase-1 that, in turn, leads to dephosphorylation and inactivation of both MAPK JNK and p38, the negative regulators for TLR2 induction.


These results indicate that glucocorticoids not only suppress immune and inflammatory response, but also enhance the expression of the host defense receptor, TLR2. Thus, our 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 MAPK.

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