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2019 ; 10
(ä): 2798
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A Biodegradable Mg-Based Alloy Inhibited the Inflammatory Response of THP-1
Cell-Derived Macrophages Through the TRPM7-PI3K-AKT1 Signaling Axis
#MMPMID31849975
Jin L
; Chen C
; Li Y
; Yuan F
; Gong R
; Wu J
; Zhang H
; Kang B
; Yuan G
; Zeng H
; Chen T
Front Immunol
2019[]; 10
(ä): 2798
PMID31849975
show ga
Mg-based alloys might be ideal biomaterials in clinical applications owing to
favorable mechanical properties, biodegradability, biocompatibility, and
especially their anti-inflammatory properties. However, the precise signaling
mechanism underlying the inhibition of inflammation by Mg-based alloys has not
been elucidated. Here, we investigated the effects of a Mg-2.1Nd-0.2Zn-0.5Zr
alloy (denoted as JDBM) on lipopolysaccharide (LPS)-induced macrophages. THP-1
cell-derived macrophages were cultured on JDBM, Ti-6Al-4V alloy (Ti), 15% extract
of JDBM, and 7.5 mM of MgCl(2) for 1 h before the addition of LPS for an
indicated time; the experiments included negative and positive controls. Our
results showed JDBM, extract, and MgCl(2) could decrease LPS-induced tumor
necrosis factor (TNF) and interleukin (IL)-6 expression. However, there were no
morphologic changes in macrophages on Ti or JDBM. Mechanically, extract and
MgCl(2) downregulated the expression of toll-like receptor (TLR)-4 and MYD88
compared with the positive control and inhibited LPS-induced nuclear factor-kappa
B (NF-?B) and mitogen-activated protein kinase (MAPK) signaling pathways by
inactivation of the phosphorylation of IKK-?/?, IK?-?, P65, P38, and JNK.
Additionally, the LPS-induced reactive oxygen species (ROS) expression was also
decreased by extract and MgCl(2). Interestingly, the expression of LPS-induced
TNF and IL-6 could be recovered by knocking down TRPM7 of macrophages, in the
presence of extract or MgCl(2). Mechanically, the activities of AKT and AKT1 were
increased by extract or MgCl(2) with LPS and were blocked by a PI3K inhibitor,
whereas siRNA TRPM7 inhibited only AKT1. Together, our results demonstrated the
degradation products of Mg-based alloy, especially magnesium, and resolved
inflammation by activation of the TRPM7-PI3K-AKT1 signaling pathway, which may be
a potential advantage or target to promote biodegradable Mg-based alloy
applications.