Rui Yamaguchi
   Department   Kumamoto Health Science University  Department of Medical Technology, Faculty of Health Science
   Kumamoto Health Science University Graduate School  Division of Health Sciences, Graduate School of Health Sciences
   Position   Associate Professor
Language English
Publication Date 2015/06
Type
Peer Review Peer reviewed
Title Mechanism of interleukin-13 production by granulocyte-macrophage colony-stimulating factor-dependent macrophages via protease-activated receptor-2
Contribution Type
Journal Blood Cells Mol Dis.
Journal TypeAnother Country
Volume, Issue, Page 55,pp.21-26
Total page number 5
Authorship Lead author
Author and coauthor Yamaguchi R, Yamamoto T, Sakamoto A, Ishimaru Y, Narahara S, Sugiuchi H, Hirose E, Yamaguchi Y
Details Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes classically activated M1 macrophages. GM-CSF upregulates protease-activated receptor-2 (PAR-2) protein expression and activation of PAR-2 by human neutrophil elastase (HNE) regulates cytokine production.
PAR-2 protein was detected in GM-CSF-dependent macrophages by Western blotting. Unexpectedly, PD98059 (an ERK1 inhibitor) increased IL-13 production, even at higher concentrations. Interestingly, U0126 (an ERK1/2 inhibitor) reduced IL-13 production in a concentration-dependent manner. Neither SB203580 (a p38alpha/p38beta inhibitor) nor BIRB796 (a p38gamma/p38delta inhibitor) affected IL-13 production, while TMB-8 (a calcium chelator) diminished IL-13 production.Stimulation with HNE promoted the production of IL-13 (a Th2 cytokine) by GM-CSF-dependent M1 macrophages. PAR-2-mediated IL-13 production may be dependent on the Ca(2+)/ERK2 signaling pathway.