Effect of rottlerin, a PKC-delta inhibitor, on TLR-4-dependent activation of murine microglia
SCIE
SCOPUS
- Title
- Effect of rottlerin, a PKC-delta inhibitor, on TLR-4-dependent activation of murine microglia
- Authors
- Kim, DC; Kim, SH; Jeong, MW; Baek, NI; Kim, KT
- Date Issued
- 2005-11-11
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Abstract
- In microglia, Toll-like receptors have been shown to recognize pathogen-associated molecular patterns and initiate innate immune responses upon interaction with infectious agents. The effect of rottlerin, a PKC-delta specific inhibitor, on TLR-4-mediated signaling was investigated in murine microglia stimulated with lipopolysaccharide and taxol. Pretreatment of microglia cells with rottlerin decreased LPS- and taxol-induced nitric oxide production in a concentration-dependent manner (IC50 = 99.1 +/- 1.5 nM). Through MTT and FACS analysis, we found that the inhibition effect of rottlerin was not due to microglial cell death. Rottlerin pretreatment also attenuated LPS-induced phosphorylation of IkappaB-alpha, nuclear translocation of NF-kappa B, and expression of type 11 nitric oxide synthase. In addition, microglial phagocytosis in response to TLR-4 activation was diminished in which rottlerin was pretreated. Together, these data raise the possibility that certain PKC-delta specific inhibitors can modulate TLR-4-derived signaling and inflammatory target gene expression, and can alter susceptibility to microbial infection and chronic inflammatory diseases in central nervous system. (c) 2005 Elsevier Inc. All rights reserved.
- Keywords
- rottlerin; microglia; TLR-4; nitric oxide; phagocytosis; PROTEIN-KINASE-C; KAPPA-B ACTIVATION; NITRIC-OXIDE; CELLS; EXPRESSION; BRAIN; LIPOPOLYSACCHARIDE; DIFFERENTIATION; MODULATION; INDUCTION
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/24350
- DOI
- 10.1016/j.bbrc.2005.09.009
- ISSN
- 0006-291X
- Article Type
- Article
- Citation
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 337, no. 1, page. 110 - 115, 2005-11-11
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