geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Phosphatidylinositol 3-kinase is involved in Toll-like receptor 4-mediated cytokine expression in mouse macrophages


, : Phosphatidylinositol 3-kinase is involved in Toll-like receptor 4-mediated cytokine expression in mouse macrophages. European Journal of Immunology 33(3): 597-605

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.

US$19.90

PMID: 12616480

DOI: 10.1002/eji.200323376


Other references

Moragianni, V.A.; Cohen, J.D.; Smith, S.J.; Rosenn, M.F.; Craparo, F.J., 2010: The role of ultrasound-indicated cerclage in triplets. Preterm delivery is the leading cause of major perinatal morbidity and mortality associated with triplet pregnancies. The objective of this study was to evaluate the efficacy of ultrasound-indicated cervical cerclage in triplet pregnancies that ar...

Tam, P.E.; Messner, R.P., 1997: Coxsackievirus-induced chronic inflammatory myopathy: virus variants distinguish between acute cytopathic effects and pathogenesis of chronic disease. Infection with the Tucson strain of coxsackievirus B1 (CVB1-T) causes the development of chronic inflammatory myopathy (CIM) and hind limb weakness in susceptible strains of mice. In this study, a panel of six plaque-purified viruses exhibiting ei...

Smith, F.F.; Fulton, R.A.; Edwards, F.I., 1952: New insecticides for greenhouse vegetables. Advice is given on the control of 21 common pests of greenhouse vegetables with TEPP, sulfotepp, parathion, DDT and lindane.

Joysey K.A., 1978: Protein sequences a phylogenetic dream or nightmare. Biological Journal Of The Linnean Society: 440

Dhople, Arvind M., 1997: Comparative in vitro and in vivo activities of rifamycin analogs against Mycobacterium leprae. Abstracts of the Interscience Conference on Antimicrobial Agents & Chemotherapy 37: 143

Seggelke, K.; Obenaus, F.; Rosenwinkel, K.H., 1999: Dynamic simulation of a low loaded trickling filter for nitrification. For this report, an existing biofilm model was examined in regard to its suitability for the simulation of full scale trickling filter for nitrification. The system was calibrated using the results ascertained in a measuring campaign under dry wea...

Chang, Y.O.; Varnell, T.R., 1977: Effect of dietary carbohydrates on intestinal transport and accumulation of iron 59 ion in iron deficient rats. Laboratory rats were fed several types of carbohydrates incorporated into Fe-deficient diets. The lowest active transport of 59Fe2+ across the intestinal wall and the lowest intestinal accumulation of 59Fe occurred in rats fed dextrin or fructose,...

Joshi S.; Kozlowski M., 1987: Secretion and properties of serratia liquefaciens chitinases. Abstracts of Papers American Chemical Society 193

Sai Prasad, T.R.; Low, Y.; Tan, C.E.; Jacobsen, A.S., 2006: Swallowed foreign bodies in children: report of four unusual cases. Introduction: Although a majority of ingested foreign bodies (FBs) pass down the gastrointestinal tract spontaneously, those that are sharp, pointed or large in size need removal to avert serious complications. We highlight the urgent need and uti...

Kraszpulski, J., 1969: Indication and practical recommendations in prosthetic treatment of prisoners. Protetyka Stomatologiczna 19(4): 223-230