Identification of a role for the PI3K/AKT/mTOR signaling pathway in innate immune cells.
The innate immune system is the first line of host defense against infection and involves several different cell types. Here we investigated the role of the phosphatidylinositol 3 kinase (PI3K) signaling pathway in innate immune cells. By blocking this pathway with pharmacological inhibitors, we found that the production of proinflammatory cytokines was drastically suppressed in monocytes and macrophages. Further study revealed that the suppression was mainly related to the mammalian target of rapamycin (mTOR)/p70(S6K) signaling. In addition, we found that the PI3K pathway was involved in macrophage motility and neovascularization. Our data provide a rationale that inhibition of the PI3K signaling pathway could be an attractive approach for the management of inflammatory disorders.
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
Songbo
S
Xie
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
Miao
M
Chen
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
Bing
B
Yan
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
Xianfei
X
He
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
Xiwen
X
Chen
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
Dengwen
D
Li
D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D016207:Cytokines; D018836:Inflammation Mediators; D047428:Protein Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D058539:Phosphatidylinositol 3-Kinase; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D038362:Glycogen Synthase Kinase 3