A negative regulator or just an unconcerned passerby: phosphoinositide 3-kinase signalling in IL-12 production.
Pathogens are eliminated from the host by the cooperative functions of the innate and adaptive immune systems, where interleukin 12 (IL-12) plays a crucial role. As overactivity of IL-12 can lead to autoimmune-mediated tissue damage, IL-12 production is tightly regulated. Notably, the phosphoinositide 3-kinase (PI3K) pathway suppresses Toll-like receptor (TLR)-induced IL-12 production as an auto-inhibitory regulator in dendritic cells. However, Okazaki et al. (C5a controls TLR-induced IL-10 and IL-12 production independent of phosphoinositide 3-kinase. J. Biochem. 2011;149:265-274) recently indicated that PI3K activated downstream of C5a anaphylatoxin does not affect the induction of IL-12 by TLR, although C5a efficiently inhibits the induction, in macrophages. PI3K is thus a context-dependent regulator of TLR-mediated IL-12 production.
Department of Biochemistry, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan. keiji-miyazawa@umin.ac.jp
Keiji
K
Miyazawa
D000818:Animals; D003165:Complement System Proteins / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D018664:Interleukin-12 / Q000096:biosynthesis*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism
D051193:Toll-Like Receptors; D018664:Interleukin-12; D003165:Complement System Proteins; D019869:Phosphatidylinositol 3-Kinases