Back to Search
Start Over
Phosphatidylinositol 3-kinase is involved in Toll-like receptor 4-mediated cytokine expression in mouse macrophages
- Source :
- European journal of immunology. 33(3)
- Publication Year :
- 2003
-
Abstract
- Recent evidence suggests a role for phosphatidylinositol (PI) 3-kinase in various inflammatory responses. In this study, the consequences of LPS-induced PI 3-kinase activation on cytokine and chemokine expression and the intracellular mechanisms of inflammatory activation were examined in mouse macrophages. LPS stimulation induced a complex formation between PI 3-kinase and myeloid differentiation factor 88 (MyD88), which was followed by an induction of IL-1beta, tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein (MIP)-2. The induction of IL-1beta, but not of MIP-2 or TNF-alpha, was blocked by the PI 3-kinase inhibitors LY294002 and wortmannin. The nuclear factor-kappaB (NF-kappaB) inhibitor pyrrolidinedithiocarbamate (PDTC) blocked the induction of IL-1beta and TNF-alpha, but had no effect on MIP-2 expression. Inhibition of PI 3-kinase decreased the LPS-induced transcriptional activity of NF-kappaB, but it had no effect on the nuclear DNA binding activity of NF-kappaB. These findings suggest that, while NF-kappaB nuclear localization and DNA binding are necessary, they are not sufficient for transcriptional activation of the IL-1beta gene in the absence of PI 3-kinase activity. Taken together, our results demonstrate that activation of Toll-like receptor (TLR)-4 results in PI 3-kinase-MyD88 complex formation, and that PI 3-kinase activity selectively leads to cytokine induction downstream of TLR4.
- Subjects :
- Lipopolysaccharides
medicine.medical_treatment
Immunology
Receptors, Cell Surface
Biology
Protein Serine-Threonine Kinases
Wortmannin
chemistry.chemical_compound
Mice
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins
medicine
Immunology and Allergy
Animals
Drosophila Proteins
LY294002
Phosphatidylinositol
RNA, Messenger
Receptors, Immunologic
Macrophage inflammatory protein
Cells, Cultured
Adaptor Proteins, Signal Transducing
Toll-like receptor
Membrane Glycoproteins
Kinase
Macrophages
Toll-Like Receptors
NF-kappa B
Antigens, Differentiation
Cell biology
Toll-Like Receptor 4
Cytokine
chemistry
Myeloid Differentiation Factor 88
TLR4
Cytokines
Proto-Oncogene Proteins c-akt
Subjects
Details
- ISSN :
- 00142980
- Volume :
- 33
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- European journal of immunology
- Accession number :
- edsair.doi.dedup.....973d67c25911c4c2b27ed1242a5a0b11