Effects of a CCR2 antagonist on macrophages and Toll-like receptor 9 expression in a mouse model of diabetic nephropathy
Seigo Ito, Hiroyuki Nakashima, Takuya Ishikiriyama, Masahiro Nakashima, Akira Yamagata, Toshihiko Imakiire, Manabu Kinoshita, Shuhji Seki, Hiroo Kumagai, Naoki Oshima
Abstract
We classified kidney macrophages (Mφs) into bone marrow-derived Mφs (BM-Mφs) expressing high CD11b and tissue-specific resident Mφ (Res-Mφs) expressing low CD11b. In diabetic nephropathy (DN) model mice, Toll-like receptor 9 (TLR9) expression and TNF-α production via TLR9 activation in BM-Mφs and ROS production in Res-Mφs were enhanced. Furthermore, CCR2 antagonist suppressed the kidney infiltration of BM-Mφs and their function and the ROS production by Res-Mφs, with concomitant TLR9 suppression. Our study presents a new therapeutic strategy for DN.
Topics & Concepts
TLR9Diabetic nephropathyTLR2EndocrinologyInternal medicineBone marrowInflammationPathogenesisTumor necrosis factor alphaKidneyBiologyMedicineTLR4Gene expressionDNA methylationBiochemistryGeneImmune cells in cancerImmune Response and InflammationAdvanced Glycation End Products research