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PI 3K Inhibitors LY 294002 and IC 87114 Reduce Inflammation in Carrageenan‐Induced Paw Oedema and Down‐Regulate Inflammatory Gene Expression in Activated Macrophages
Author(s) -
Eräsalo Heikki,
Laavola Mirka,
Hämäläinen Mari,
Leppänen Tiina,
Nieminen Riina,
Moilanen Eeva
Publication year - 2015
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12284
Subject(s) - ly294002 , inflammation , pi3k/akt/mtor pathway , carrageenan , protein kinase b , pharmacology , in vivo , chemistry , signal transduction , phosphorylation , gene expression , cancer research , microbiology and biotechnology , biology , immunology , gene , biochemistry
PI3K/Akt pathway is a well‐characterized pathway controlling cellular processes such as proliferation, migration and survival, and its role in cancer is vastly studied. There is also evidence to suggest the involvement of this pathway in the regulation of inflammatory responses. In this study, an attempt was made to investigate the role of PI3Ks in acute inflammation in vivo using pharmacological inhibitors against PI3Ks in the carrageenan‐induced paw oedema model. A non‐selective PI3K inhibitor LY294002 and a PI3Kδ‐selective inhibitor IC87114 were used. Both of these inhibitors reduced inflammatory oedema upon carrageenan challenge in the mouse paw. To explain this result, the effects of the two inhibitors on inflammatory gene expression were investigated in activated macrophages. LY294002 and IC87114 prevented Akt phosphorylation as expected and down‐regulated the expression of inflammatory factors IL‐6, MCP‐1,TNFα and iNOS . These findings suggest that PI3K inhibitors could be used to attenuate inflammatory responses and that the mechanism of action behind this effect is the down‐regulation of inflammatory gene expression.