1,25-Dihydroxyvitamin D<sub>3</sub>Promotes High Glucose-Induced M1 Macrophage Switching to M2 via the VDR-PPAR<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:mi mathvariant="bold-italic">γ</mml:mi></mml:mrow></mml:math>Signaling Pathway

Zhang, Xiaoliang; Zhou, Min; Guo, Yinfeng; Song, Zhixia; Liu, Bi‐Cheng

doi:10.1155/2015/157834

Cited by 74 publications

(71 citation statements)

References 37 publications

(43 reference statements)

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“…This study shows, at least in part, that geraniin is an effective drug for inhibiting LPS-induced M1 macrophage polarization. M1 macrophages release pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β and produce toxic NO and induce the activity of iNOS [24], which aggravate inflammation creating a vicious negative feedback loop. Fig.…”

Section: Discussionmentioning

confidence: 99%

Geraniin Inhibits LPS-Induced THP-1 Macrophages Switching to M1 Phenotype via SOCS1/NF-κB Pathway

Liu

Peng

et al. 2016

Inflammation

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M1 macrophage polarization is proved to promote inflammation in atherosclerosis process. In this study, we evaluated the inhibitory effect of geraniin, a bioactive polyphenolic compound, on the LPS-induced switch of THP-1 macrophages to M1 phenotype, and we propose a molecular basis for its action. Flow cytometry analysis indicated that geraniin significantly inhibited LPS-induced M1 macrophage polarization. Geraniin downregulated the protein and the mRNA level of typical cytokines of M1 macrophage, including tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), indicating that geraniin can suppress typical mediators of M1 macrophage at the transcriptional level. Moreover, geraniin inhibited LPS-induced reactive oxygen species (ROS) and nitric oxide (NO) production, as well as inducible nitric oxide synthase (iNOS) activity, in THP-1 macrophages. Furthermore, western blot analysis indicated that geraniin decreased both LPS-induced phosphorylation of NF-κB-p65 and NF-κB-p65 expression without affecting the level of IκB-α. This suggested that geraniin inhibited NF-κB, a transcription factor pivotal in the LPS-induced expression of pro-inflammatory genes and an important player in M1 macrophage polarization. Moreover, an electrophoretic mobility shift assay (EMSA) demonstrated that geraniin blocked the LPS-induced translocation of NF-κB to the nucleus. Moreover, we found that geraniin up-regulated the expression of SOCS1, an upstream regulator of NF-κB activation that can directly bind to NF-κB-p65 and downregulate it, thus inhibiting NF-κB activation. In conclusion, geraniin inhibits LPS-induced THP-1 macrophages switching to M1 phenotype through SOCS1/NF-κB pathway.

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Section: Discussionmentioning

confidence: 99%

Geraniin Inhibits LPS-Induced THP-1 Macrophages Switching to M1 Phenotype via SOCS1/NF-κB Pathway

Liu

Peng

et al. 2016

Inflammation

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“…Furthermore, 1,25(OH) 2 D 3 inhibits Th17 immune responses possibly through its capacity to inhibit IL-6 and IL-23 production and induces reciprocal differentiation of Foxp3 + Treg cells [17]. The activity of 1,25(OH) 2 D 3 is mediated by vitamin D receptor (VDR) and 1,25(OH) 2 D 3 promotes M1 macrophages phenotype switching to M2 via the VDR-PPARγ pathway [18]. However, the effect of 1,25(OH) 2 D 3 on NK-cell immunity has not been studied well.…”

Section: Introductionmentioning

confidence: 99%

1,25‐Dihydroxy‐vitamin D3 regulates NK‐cell cytotoxicity, cytokine secretion, and degranulation in women with recurrent pregnancy losses

et al. 2015

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Vitamin D has a pivotal role in regulating immune responses by promoting Th2 immune responses and suppressing Th1 responses. Propensities to a Th1 immune response and increased NK-cell levels and cytotoxicity have been reported in women with recurrent pregnancy losses (RPL). In women with RPL, vitamin D deficiency is prevalent IntroductionVitamin D is a group of secosteroids and has a major role in maintaining skeletal health. Various effects of vitamin D on extra skeletal tissues have been reported as well, during the past decade [1]. Vitamin D deficiency is endemic for both men and women and across different age groups in the US population [2]. Low C 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2015. 45: 3188-3199 Clinical immunology 3189vitamin D level has been linked to major common health problems in populations, particularly inflammatory conditions such as cardiovascular disease, cancers, diabetes, autoimmune diseases including multiple sclerosis, rheumatoid arthritis, and others [3]. In addition, vitamin D deficiency is a predisposing factor for various female diseases such as osteoporosis, uterine fibroids, endometriosis, and breast cancer and a risk factor for obstetrical complications such as gestational diabetes and preeclampsia [4,5]. Recently, we have reported that 47.4% of women with recurrent pregnancy losses (RPL) have vitamin D deficiency [6]. In women with RPL, decreased vitamin D level was associated with the increased prevalence of antiphospholipid antibody, antinuclear antigen antibody, anti-ssDNA, and anti-thyroperoxidase antibody. In addition, peripheral blood CD19 + B and CD56 + NK-cell levels and NK cytotoxicity were significantly higher in women with low vitamin D level when compared with those of normal vitamin D level [6]. Normal pregnancy is associated with Th2 shift in T-cell immunity [7]. The comparable shift in NK-cell immunity has been reported during normal pregnancy including a bias to NKr1 that produce IL-10 in peripheral blood, and NK3 cells that produce TGF-β in decidual NK cells [8]. Additionally, decidual innate lymphoid cell 3 (ILC3) may play a role in innate defenses, and vessel and tissue rebuilding, thus contributing to maintenance of pregnancy [9]. Contrarily, a propensity to Th1 immune response and increased NK-cell levels and cytotoxicity have been reported in women with RPL and multiple implantation failures (MIF) after in vitro fertilization and embryo transfer cycles [10]. Women with miscarriages and preeclampsia as well, have NK1 and NKT1 shift that produce high amounts of IFN-γ and little IL-4 in peripheral blood [11]. Therefore, cellular immune-regulation including innate immunity is critical for human reproduction.Women with RPL and MIF have significantly higher NK-cell levels and cytotoxicity, and dysregulated cytokine production patterns as compared to normal controls [10,12]. Activating receptor expression on NK cells was significantly increased, while inhibitory receptor expression was significantly decreased in ...

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“…In a rat model of diabetic nephropathy, 1,25(OH) 2 D 3 inhibited M1 macrophage activation, inflammation and renal injury while it enhanced M2 activation [26]. In another study, 1,25(OH) 2 D 3 suppressed high-glucose-induced M1 activation of rat macrophages while it enhanced M2 activation [27]. Our study, together with these studies, demonstrates that the active form of vitamin D promotes M1 phenotype switching to M2, providing a basis for therapeutic intervention.…”

Section: Discussionmentioning

confidence: 99%

1,25-Dihydroxyvitamin D<sub>3</sub> Facilitates M2 Polarization and Upregulates TLR10 Expression on Human Microglial Cells

Verma

Kim²

2016

Neuroimmunomodulation

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Objective: To explore the effects of 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃], the active metabolite of vitamin D, on M1/M2 polarization of human microglia and the expression of Toll-like receptor 10 (TLR10) on these cells, which has been suggested to play an inhibitory role in inflammation previously. Methods: Microglial HMO6 cells were treated with 1,25(OH)₂D₃, and mRNA or protein levels of M1 and M2 cytokines and TLR10 were examined. Results: 1,25(OH)₂D₃ upregulated TLR10 in HMO6 cells at both mRNA and protein level. 1,25(OH)₂D₃ enhanced basal mRNA expression of M2 cytokines, such as IL-10 and CCL17, but did not affect the expression of M1 cytokines, including IL-12 and TNF-α. 1,25(OH)₂D₃ downregulated the lipopolysaccharide (LPS)-induced mRNA expression of M1 cytokines IL-12 and TNF-α. Concomitantly, it upregulated not only the M2 cytokines IL-10 and CCL17, but also TLR10 in microglial cells treated with LPS, in a concentration-dependent manner. Conclusions: Our results suggest that 1,25(OH)₂D₃ may exert anti-inflammatory action by facilitating the M2 polarization of human microglial cells.

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1,25-Dihydroxyvitamin D₃Promotes High Glucose-Induced M1 Macrophage Switching to M2 via the VDR-PPARγSignaling Pathway

Cited by 74 publications

References 37 publications

Geraniin Inhibits LPS-Induced THP-1 Macrophages Switching to M1 Phenotype via SOCS1/NF-κB Pathway

Geraniin Inhibits LPS-Induced THP-1 Macrophages Switching to M1 Phenotype via SOCS1/NF-κB Pathway

1,25‐Dihydroxy‐vitamin D3 regulates NK‐cell cytotoxicity, cytokine secretion, and degranulation in women with recurrent pregnancy losses

1,25-Dihydroxyvitamin D<sub>3</sub> Facilitates M2 Polarization and Upregulates TLR10 Expression on Human Microglial Cells

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1,25-Dihydroxyvitamin D3Promotes High Glucose-Induced M1 Macrophage Switching to M2 via the VDR-PPARγSignaling Pathway

Cited by 74 publications

References 37 publications

Geraniin Inhibits LPS-Induced THP-1 Macrophages Switching to M1 Phenotype via SOCS1/NF-κB Pathway

Geraniin Inhibits LPS-Induced THP-1 Macrophages Switching to M1 Phenotype via SOCS1/NF-κB Pathway

1,25‐Dihydroxy‐vitamin D3 regulates NK‐cell cytotoxicity, cytokine secretion, and degranulation in women with recurrent pregnancy losses

1,25-Dihydroxyvitamin D<sub>3</sub> Facilitates M2 Polarization and Upregulates TLR10 Expression on Human Microglial Cells

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1,25-Dihydroxyvitamin D₃Promotes High Glucose-Induced M1 Macrophage Switching to M2 via the VDR-PPARγSignaling Pathway