Abstract
In our previous report, M2-macrophage (Mφs) deficient mice showed increased renal calcium oxalate (CaOx) crystal formation; however, the role of Mφs-related-cytokines and chemokines that affect kidney stone formation remains unknown. Here, we investigated the role of M1/M2s in crystal development by using in vitro and in vivo approaches. The crystal phagocytic rate of bone marrow-derived M2Mφs was higher than that of bone marrow-derived Mφs and M1Mφs and increased on co-culture with renal tubular cells (RTCs). However, the amount of crystal attachment on RTCs reduced on co-culture with M2Mφs. In six hyperoxaluric C57BL/6J mice, M1Mφ transfusion and induction by LPS and IFN-γ facilitated renal crystal formation, whereas M2Mφ transfusion and induction by IL-4 and IL-13 suppressed renal crystal formation compared with the control. These M2Mφ treatments reduced the expression of crystal-related genes, such as osteopontin and CD44, whereas M1Mφ treatment increased the expression of pro-inflammatory and adhesion-related genes such as IL-6, inducible NOS, TNF-α, C3, and VCAM-1. The expression of M2Mφ-related genes was lower whereas that of M1Mφ-related genes was higher in papillary tissue of CaOx stone formers. Overall, our results suggest that renal crystal development is facilitated by M1Mφs, but suppressed by M2Mφs.
Highlights
In our previous report, M2-macrophage (Mφs) deficient mice showed increased renal calcium oxalate (CaOx) crystal formation; the role of Mφs-related-cytokines and chemokines that affect kidney stone formation remains unknown
An in vitro study demonstrated that the co-culture of renal tubular cells (RTCs) and RAW 264.7, a murine Mφcell line, facilitates the adherence of CaOx monohydrate (COM) crystals on RTCs via the expression of pro-inflammatory adipocytokines such as monocyte chemoattractant protein 1 (MCP-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF)-α
We found that colony stimulating factor (CSF)-1 signaling suppressed renal crystal formation by the induction of M2-like Mφsin M2-deficient mice, revealing the potential therapeutic role of M2s and the differentiation of M1s23
Summary
M2-macrophage (Mφs) deficient mice showed increased renal calcium oxalate (CaOx) crystal formation; the role of Mφs-related-cytokines and chemokines that affect kidney stone formation remains unknown. Our previous studies showed spontaneous disappearance of renal calcium oxalate (CaOx) crystals in hyperoxaluric mice with the expression of various Mφ-related cytokines and chemokines. An in vitro study demonstrated that the co-culture of renal tubular cells (RTCs) and RAW 264.7, a murine Mφcell line, facilitates the adherence of COM crystals on RTCs via the expression of pro-inflammatory adipocytokines such as monocyte chemoattractant protein 1 (MCP-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF)-α. We investigated the role of M1Mφsand M2Mφsin renal CaOx crystal development using ex vivo induction of bone-derived Mφs (BMMs) with both in vitro and in vivo approaches.
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