Open AccessEffects of a CCR2 antagonist on macrophages and Toll-like receptor 9 expression in a mouse model of diabetic nephropathy
Author(s) -
Seigo Itô,
Hiroyuki Nakashima,
Takuya Ishikiriyama,
Masahiro Nakashima,
Akira Yamagata,
Toshihiko Imakiire,
Manabu Kinoshita,
Shu Seki,
Hiroo Kumagai,
Naoki Oshima
Publication year - 2021
Publication title -
american journal of physiology. renal physiology./american journal of physiology. renal physiology
Language(s) - English
Resource type - Journals
eISSN - 1931-857X
pISSN - 1522-1466
DOI - 10.1152/ajprenal.00191.2021
Subject(s) - tlr9 , diabetic nephropathy , tlr2 , endocrinology , medicine , bone marrow , inflammation , pathogenesis , tumor necrosis factor alpha , kidney , biology , tlr4 , gene expression , biochemistry , gene , dna methylation
We classified kidney macrophages (Mφs) into bone marrow-derived (BM-) macrophages expressing high CD11b and tissue-specific resident (Res-) macrophages expressing low CD11b. In diabetic nephropathy (DN) model mice, 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.