Protumoral TSP50 Regulates Macrophage Activities and Polarization via Production of TNF-α and IL-1β, and Activation of the NF-κB Signaling Pathway

Yang, Cheng; Zhang, Dongmei; Hou, Yaqin; Bao, Yongli; Sun, Luguo; Yu, Chunlei; Li, Yuxin

doi:10.1371/journal.pone.0145095

Cited by 15 publications

(9 citation statements)

References 42 publications

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“…Wnt/ β -catenin and notch signaling are known to promote M2 macrophage polarization and signaling through IL-4 and IL-13 [25–27]. Yang et al reported that the testes-specific protease 50 modulates macrophages and induces M2 polarization via TNF- α , IL-1 β , and NF- κ B signaling pathways [28]. Recently, the transcription factors MafB, Klf4, and Stat6 have been reported to promote M2 polarization by inducing the genes related to anti-inflammatory functions [29–31].…”

Section: Discussionmentioning

confidence: 99%

Adipose-Derived Mesenchymal Stem Cells Promote M2 Macrophage Phenotype through Exosomes

Heo

Choi

Kim

2019

Stem Cells International

113

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Accumulating evidence has shown that the paracrine factors derived from mesenchymal stem cells (MSCs) are capable of regulating the immune system via interaction with various immune cells. In this study, adipose-derived MSCs (AdMSCs) and human peripheral blood monocytes (PBMCs) were isolated and cultured to examine the effects of MSC-induced macrophages (iMΦ) on inflammation and immune modulation. Indirect coculture with MSCs increased the expression of arginase-1 and mannose receptor (CD206), markers of activated M2 macrophages, in the PBMCs demonstrating that MSC-secreted factors promoted M2-MΦ polarization. Additionally, iMΦ exhibited a similar higher inhibitory effect on the growth of activated T cells compared to that in the other groups (AdMSCs only, AdMSCs plus iMΦ), implying that iMΦ can play a sufficient functional role. Interestingly, the population of FoxP3 Treg cells significantly increased when cocultured with iMΦ, suggesting that iMΦ have an immunomodulatory effect on the Treg cells through the modulation of the FoxP3 expression. Notably, iMΦ expressed high levels of immunosuppressive and anti-inflammatory cytokines, namely IL-10 and TSG-6. Furthermore, we confirmed that the AdMSC-derived exosomes modulated macrophage polarization by upregulating the expression of M2 macrophage markers. Conclusively, our results suggest that iMΦ play a significant role in regulating the immunomodulatory- and inflammatory-mediated responses. Thus, iMΦ may be used as a novel stem cell-based cell-free therapy for the treatment of immune-mediated inflammatory disorders.

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Section: Discussionmentioning

confidence: 99%

Adipose-Derived Mesenchymal Stem Cells Promote M2 Macrophage Phenotype through Exosomes

Heo

Choi

Kim

2019

Stem Cells International

113

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“…Total RNA (3 μg) was reverse transcribed into cDNA according to instructions. The target genes were then amplified by RT-PCR or RT-qPCR with corresponding primers ( Table 1 ) as described previously [ 32 ].…”

Section: Methodsmentioning

confidence: 99%

“…Whole cell extracts or cytosolic and nuclear extracts were prepared as previously described [ 32 , 33 ]. The extracts were then resolved by 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), transferred to a polyvinylidene fluoride (PVDF) membrane, and sequentially probed with various primary antibodies and horseradish peroxidase (HRP)-conjugated secondary antibodies for 1 h at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Stevioside Activates AMPK to Suppress Inflammation in Macrophages and Protects Mice from LPS-Induced Lethal Shock

Wei

Zhu

et al. 2021

Molecules

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Stevioside, a diterpenoid glycoside, is widely used as a natural sweetener; meanwhile, it has been proven to possess various pharmacological properties as well. However, until now there were no comprehensive evaluations focused on the anti-inflammatory activity of stevioside. Thus, the anti-inflammatory activities of stevioside, both in macrophages (RAW 264.7 cells, THP-1 cells, and mouse peritoneal macrophages) and in mice, were extensively investigated for the potential application of stevioside as a novel anti-inflammatory agent. The results showed that stevioside was capable of down-regulating lipopolysaccharide (LPS)-induced expression and production of pro-inflammatory cytokines and mediators in macrophages from different sources, such as IL-6, TNF-α, IL-1β, iNOS/NO, COX2, and HMGB1, whereas it up-regulated the anti-inflammatory cytokines IL-10 and TGF-β1. Further investigation showed that stevioside could activate the AMPK -mediated inhibition of IRF5 and NF-κB pathways. Similarly, in mice with LPS-induced lethal shock, stevioside inhibited release of pro-inflammatory factors, enhanced production of IL-10, and increased the survival rate of mice. More importantly, stevioside was also shown to activate AMPK in the periphery blood mononuclear cells of mice. Together, these results indicated that stevioside could significantly attenuate LPS-induced inflammatory responses both in vitro and in vivo through regulating several signaling pathways. These findings further strengthened the evidence that stevioside may be developed into a therapeutic agent against inflammatory diseases.

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“…Total proteins and cytosolic-nuclear proteins were extracted as previously described [ 29 ]. The extracts were electro-blotted onto a polyvinylidene fluoride (PVDF) membrane following separation by 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE).…”

Section: Methodsmentioning

confidence: 99%

Ginkgolide A Ameliorates LPS-Induced Inflammatory Responses In Vitro and In Vivo

Yao

et al. 2017

IJMS

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Ginkgolide A (GA) is a natural compound isolated from Ginkgo biloba and has been used to treat cardiovascular diseases and diabetic vascular complications. However, only a few studies have been conducted on the anti-inflammatory effects of GA. In particular, no related reports have been published in a common inflammation model of lipopolysaccharide (LPS)-stimulated macrophages, and the anti-inflammatory mechanisms of GA have not been fully elucidated. In the present study, we extensively investigated the anti-inflammatory potential of GA in vitro and in vivo. We showed that GA could suppress the expression of pro-inflammatory mediators (cyclooxygenase-2 (COX-2) and nitric oxide (NO) and pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β) in LPS-treated mouse peritoneal macrophages, mouse macrophage RAW264.7 cells, and differentiated human monocytes (dTHP-1) in vitro. These effects were partially carried out via downregulating Nuclear factor kappa-B (NF-κB), Mitogen-activated protein kinases (MAPKs) (p38 mitogen-activated protein kinase and extracellular signal-regulated kinase (ERK), but not c-Jun N-terminal kinase (JNK), and activating the AMP-activated protein kinase (AMPK) signaling pathway also seems to be important. Consistently, GA was also shown to inhibit the LPS-stimulated release of TNF-α and IL-6 in mice. Taken together, these findings suggest that GA can serve as an effective inflammatory inhibitor in vitro and in vivo.

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Protumoral TSP50 Regulates Macrophage Activities and Polarization via Production of TNF-α and IL-1β, and Activation of the NF-κB Signaling Pathway

Cited by 15 publications

References 42 publications

Adipose-Derived Mesenchymal Stem Cells Promote M2 Macrophage Phenotype through Exosomes

Adipose-Derived Mesenchymal Stem Cells Promote M2 Macrophage Phenotype through Exosomes

Stevioside Activates AMPK to Suppress Inflammation in Macrophages and Protects Mice from LPS-Induced Lethal Shock

Ginkgolide A Ameliorates LPS-Induced Inflammatory Responses In Vitro and In Vivo

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