A Biodegradable Mg-Based Alloy Inhibited the Inflammatory Response of THP-1 Cell-Derived Macrophages Through the TRPM7–PI3K–AKT1 Signaling Axis

Jin, Liang; Chen, Chenxin; Li, Yutong; Yuan, Feng; Gong, Ruo-Lan; Wu, Jing; Zhang, Hua; Kang, Bin; Yuan, Guangyin; Zeng, Hui; Chen, Tongxin

doi:10.3389/fimmu.2019.02798

Cited by 39 publications

(23 citation statements)

References 59 publications

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“…TRPM7 kinase-deficient murine neutrophils also displayed reduced chemotaxis toward a CXCL1 gradient, which was further decreased upon TRPM7 channel blockade using NS8593, suggesting that TRPM7 channel function, at least in part, acts independent of TRPM7 kinase due to ion conductance. Previously, TRPM7 activity has already been implicated alongside PI3 kinase signaling pathways ( 10 , 45 , 46 ), however, as of now the impact of TRPM7 channel versus kinase moiety on different PI3K isoforms remains to be established. We here used PI3K isoform specific inhibitors as well as genetic inactivation of TRPM7 kinase to shed light on their interrelationship.…”

Section: Discussionmentioning

confidence: 99%

TRPM7 Kinase Is Essential for Neutrophil Recruitment and Function via Regulation of Akt/mTOR Signaling

et al. 2021

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During inflammation, neutrophils are one of the first responding cells of innate immunity, contributing to a fast clearance of infection and return to homeostasis. However, excessive neutrophil infiltration accelerates unsolicited disproportionate inflammation for instance in autoimmune diseases such as rheumatoid arthritis. The transient-receptor-potential channel-kinase TRPM7 is an essential regulator of immune system homeostasis. Naïve murine T cells with genetic inactivation of the TRPM7 enzyme, due to a point mutation at the active site, are unable to differentiate into pro-inflammatory T cells, whereas regulatory T cells develop normally. Moreover, TRPM7 is vital for lipopolysaccharides (LPS)-induced activation of murine macrophages. Within this study, we show that the channel-kinase TRPM7 is functionally expressed in neutrophils and has an important impact on neutrophil recruitment during inflammation. We find that human neutrophils cannot transmigrate along a CXCL8 chemokine gradient or produce reactive oxygen species in response to gram-negative bacterial lipopolysaccharide LPS, if TRPM7 channel or kinase activity are blocked. Using a recently identified TRPM7 kinase inhibitor, TG100-115, as well as murine neutrophils with genetic ablation of the kinase activity, we confirm the importance of both TRPM7 channel and kinase function in murine neutrophil transmigration and unravel that TRPM7 kinase affects Akt1/mTOR signaling thereby regulating neutrophil transmigration and effector function. Hence, TRPM7 represents an interesting potential target to treat unwanted excessive neutrophil invasion.

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Section: Discussionmentioning

confidence: 99%

TRPM7 Kinase Is Essential for Neutrophil Recruitment and Function via Regulation of Akt/mTOR Signaling

et al. 2021

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“…To investigate the influence of the bare and PCL-based coated AZ31 Mg alloy on the immune response, the cellular model was represented by the monocyte/macrophage cell line RAW 264.7. In the specialised literature, studies reported the use of the human monocytic cell line THP-1 [ 99 , 100 , 101 , 102 , 103 ]. However, the mouse RAW 264.7 cell line, regardless of its transformed phenotype, is generally used in inflammation studies due to its response to Escherichia coli LPS which can imitate bacterial stimuli [ 98 , 104 , 105 , 106 ].…”

Section: Discussionmentioning

confidence: 99%

In Vitro Macrophage Immunomodulation by Poly(ε-caprolactone) Based-Coated AZ31 Mg Alloy

Negrescu

Necula

Gebaur

et al. 2021

IJMS

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Due to its excellent bone-like mechanical properties and non-toxicity, magnesium (Mg) and its alloys have attracted great interest as biomaterials for orthopaedic applications. However, their fast degradation rate in physiological environments leads to an acute inflammatory response, restricting their use as biodegradable metallic implants. Endowing Mg-based biomaterials with immunomodulatory properties can help trigger a desired immune response capable of supporting a favorable healing process. In this study, electrospun poly(ε-caprolactone) (PCL) fibers loaded with coumarin (CM) and/or zinc oxide nanoparticles (ZnO) were used to coat the commercial AZ31 Mg alloy as single and combined formulas, and their effects on the macrophage inflammatory response and osteoclastogenic process were investigated by indirect contact studies. Likewise, the capacity of the analyzed samples to generate reactive oxygen species (ROS) has been investigated. The data obtained by attenuated total reflection Fourier-transform infrared (FTIR-ATR) and X-ray photoelectron spectroscopy (XPS) analyses indicate that AZ31 alloy was perfectly coated with the PCL fibers loaded with CM and ZnO, which had an important influence on tuning the release of the active ingredient. Furthermore, in terms of degradation in phosphate-buffered saline (PBS) solution, the PCL-ZnO- and secondary PCL-CM-ZnO-coated samples exhibited the best corrosion behaviour. The in vitro results showed the PCL-CM-ZnO and, to a lower extent, PCL-ZnO coated sample exhibited the best behaviour in terms of inflammatory response and receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated differentiation of RAW 264.7 macrophages into osteoclasts. Altogether, the results obtained suggest that the coating of Mg alloys with fibrous PCL containing CM and/or ZnO can constitute a feasible strategy for biomedical applications.

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“…Our previous studies reported that Mg from the degradation products of JDBM inhibited the inflammatory response of THP-1 cellderived macrophages through the TRPM7-PI3K-AKT1 signaling axis. Furthermore, Mg ions scavenged intracellular reactive oxygen species (ROS) to prevent the inflammatory response based on the LPS-induced activation of the TLR-4-MYD88-NF-κB/MAPK signaling pathway (29). However, up to now, studies on the regulation of macrophage polarization by Mg ions are still limited.…”

Section: Discussionmentioning

confidence: 99%

“…The composition of the Mg-Nd-Zn-Zr alloy ingot (denoted as JDBM), which was especially designed for vascular stents, has been described in previous studies. The composition of the biodegradable JDBM alloy is as follows (mass percent): Mg: >97%, Nd: 2.1%, Zn: 0.21%, Zr: 0.5%, Mn: 0.009%, Si: 0.006%, Cu: 0.005%, Fe: 0.002% (29)(30)(31)(32). JDBM discs (18 mm in diameter and 2.0 mm in height) were immersed in an ultrasonic cleaning bath with ethanol and acetone for 10 min and then sterilized by exposure to ultraviolet light for 1 h before use.…”

Section: Jdbm Extract Preparationmentioning

confidence: 99%

The effects of a biodegradable Mg-based alloy on the function of VSMCs via immunoregulation of macrophages through Mg-induced responses

Wu¹,

Jin²,

Tan³

et al. 2021

Ann Transl Med

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Background: Restenosis is one of the worst side effects of percutaneous coronary intervention (PCI) due to neointima formation resulting from the excessive proliferation and migration of vascular smooth muscle cells (VSMCs) and continuous inflammation. Biodegradable Mg-based alloy is a promising candidate material because of its good mechanical properties and biocompatibility, and biodegradation of cardiovascular stents.Although studies have shown reduced neointima formation after Mg-based CVS implantation in vivo, these findings were inconsistent with in vitro studies, demonstrating magnesium-mediated promotion of the proliferation and migration of VSMCs. Given the vital role of activated macrophage-driven inflammation in neointima formation, along with the well-demonstrated crosstalk between macrophages and VSMCs, we investigated the interactions of a biodegradable Mg-Nd-Zn-Zr alloy (denoted JDBM), which is especially important for cardiovascular stents, with VSMCs via macrophages.Methods: JDBM extracts and MgCl 2 solutions were prepared to study their effect on macrophages. To study the effects of the JDBM extracts and MgCl 2 solutions on the function of VSMCs via immunoregulation of macrophages, conditioned media (CM) obtained from macrophages was used to establish a VSMCmacrophage indirect coculture system.Results: Our results showed that both JDBM extracts and MgCl 2 solutions significantly attenuated the inflammatory response stimulated by lipopolysaccharide (LPS)-activated macrophages and converted macrophages into M2-type cells. In addition, JDBM extracts and MgCl 2 solutions significantly decreased the expression of genes related to VSMC phenotypic switching, migration, and proliferation in macrophages. Furthermore, the proliferation, migration, and proinflammatory phenotypic switching of VSMCs were significantly inhibited when the cells were incubated with CMs from macrophages treated with LPS + extracts or LPS + MgCl 2 solutions.Conclusions: Taken together, our results suggested that the magnesium in the JDBM extract could affect the functions of VSMCs through macrophage-mediated immunoregulation, inhibiting smooth muscle hyperproliferation to suppress restenosis after implantation of a biodegradable Mg-based stent.

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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

Cited by 39 publications

References 59 publications

TRPM7 Kinase Is Essential for Neutrophil Recruitment and Function via Regulation of Akt/mTOR Signaling

TRPM7 Kinase Is Essential for Neutrophil Recruitment and Function via Regulation of Akt/mTOR Signaling

In Vitro Macrophage Immunomodulation by Poly(ε-caprolactone) Based-Coated AZ31 Mg Alloy

The effects of a biodegradable Mg-based alloy on the function of VSMCs via immunoregulation of macrophages through Mg-induced responses

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