Human placental mesenchymal stem cells regulate inflammation via the NF‑κB signaling pathway

Liu, Youyi; Zhang, Xiading; Hu, Yiwei; Kang, Mingzhu; Wu, Yibo; Wang, Yuan; Deng, Chao

doi:10.3892/etm.2022.11591

Cited by 6 publications

(9 citation statements)

References 42 publications

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“…Knocking down the IRF3 and ISGF3 complex in myeloid cells significantly reduces inflammation and mortality in LPS-induced severe inflammation in mice 176 , 177 . MSCs can inhibit NF-kB signaling 178 - 181 , which is confirmed by our study. Additionally, we show that the MSCs synergize with A1AT to block both pathways effectively ( Figure S9 ).…”

Section: Discussionsupporting

confidence: 86%

Mesenchymal stromal cells and alpha-1 antitrypsin have a strong synergy in modulating inflammation and its resolution

Han¹,

Wu²,

Wang³

et al. 2023

Theranostics

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Rationale: Trauma, surgery, and infection can cause severe inflammation. Both dysregulated inflammation intensity and duration can lead to significant tissue injuries, organ dysfunction, mortality, and morbidity. Anti-inflammatory drugs such as steroids and immunosuppressants can dampen inflammation intensity, but they derail inflammation resolution, compromise normal immunity, and have significant adverse effects. The natural inflammation regulator mesenchymal stromal cells (MSCs) have high therapeutic potential because of their unique capabilities to mitigate inflammation intensity, enhance normal immunity, and accelerate inflammation resolution and tissue healing. Furthermore, clinical studies have shown that MSCs are safe and effective. However, they are not potent enough, alone, to completely resolve severe inflammation and injuries. One approach to boost the potency of MSCs is to combine them with synergistic agents. We hypothesized that alpha-1 antitrypsin (A1AT), a plasma protein used clinically and has an excellent safety profile, was a promising candidate for synergism. Methods: This investigation examined the efficacy and synergy of MSCs and A1AT to mitigate inflammation and promote resolution, using in vitro inflammatory assay and in vivo mouse acute lung injury model. The in vitro assay measured cytokine releases, inflammatory pathways, reactive oxygen species (ROS), and neutrophil extracellular traps (NETs) production by neutrophils and phagocytosis in different immune cell lines. The in vivo model monitored inflammation resolution, tissue healing, and animal survival. Results: We found that the combination of MSCs and A1AT was much more effective than each component alone in i) modulating cytokine releases and inflammatory pathways, ii) inhibiting ROS and NETs production by neutrophils, iii) enhancing phagocytosis and, iv) promoting inflammation resolution, tissue healing, and animal survival. Conclusion: These results support the combined use of MSCs, and A1AT is a promising approach for managing severe, acute inflammation.

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Section: Discussionsupporting

confidence: 86%

Mesenchymal stromal cells and alpha-1 antitrypsin have a strong synergy in modulating inflammation and its resolution

Han¹,

Wu²,

Wang³

et al. 2023

Theranostics

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show abstract

“…Knocking down the IRF3 and ISGF3 complex in myeloid cells significantly reduces inflammation and mortality in LPS-induced severe inflammation in mice 181,182 . MSCs can inhibit NF-kB signaling [183][184][185][186] , which is confirmed by our study. Additionally, we show that the MSCs synergize with A1AT to block both pathways effectively (fig.…”

Section: Glucocorticoids Such As Dexamethasone and Immunosuppressive ...supporting

confidence: 87%

Mesenchymal stromal cells and alpha-1 antitrypsin have a strong synergy in modulating inflammation and its resolution

Han

Wang

et al. 2022

Preprint

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Many reasons, such as infection, injury, tissue transplantation, and cancer treatment, can cause dysregulated hyperinflammation. Immune cells become excessive and hyperactive, producing sustained, systemic and large quantities of cytokines. The systemic inflammation can rapidly progress to disseminated intravascular coagulation, endothelium damage, capillary leakage, multiorgan (e.g., liver, kidney, heart, and brain) dysfunction, ARDS, and fatality. Although the initial driver may differ, the late-stage clinical features of hyperinflammation and cytokine storm converge. Unfortunately, the outcome of current treatments is still unsatisfactory. Our body has regulatory mechanisms to prevent the over-activation of immune cells, but these mechanisms fail or are insufficient in patients with hyperinflammation. Logically, augmenting these regulators represents a promising approach. Among the various natural negative regulators, mesenchymal stromal cells (MSCs) and alpha-1 antitrypsin (A1AT) are attractive due to their unique characteristics. MSCs and A1AT have shown capabilities to modulate immune cells. However, the efficacy and potency of MSCs or A1AT alone are limited and cannot fully normalize hyperinflammation and cytokine storm. Considering MSCs are cells while A1AT is a protein, we hypothesize that they may suppress inflammation using different mechanisms and have additive or synergistic effects when combined. This report showed that the combination of MSCs and A1AT was much more effective than individual components in modulating inflammation of various immune cells in vitro and in animal models. Our results provide solid evidence to support clinical studies of the combinational use of MSCs and A1AT for normalizing inflammation under various disease conditions.

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“…The concentrated solution was checked and analyzed for homogeneity using sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS–PAGE) (Li et al., 2012; Liu et al., 2018). Western blotting was conducted using the conventional technique with necessary adjustments (Liu et al., 2022).…”

Section: Methodsmentioning

confidence: 99%

“…The dialyzed solution was concentrated to 2.0 mL using a 10 kDa cut-off ultrafilter membrane (Millipore) through ultrafiltration at 8000 rpm for 20 min at 4 • C. The concentrated solution was checked and analyzed for homogeneity using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) (Li et al, 2012;Liu et al, 2018). Western blotting was conducted using the conventional technique with necessary adjustments (Liu et al, 2022).…”

Section: Purification Of Reauglu12amentioning

confidence: 99%

Expression and characterization of β‐1,3‐1,4‐glucanase of Aspergillus usamii in Escherichia coli and its application in sourdough bread making

Huang,

Zhang,

Lin

et al. 2024

Journal of Food Science

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A β‐1,3‐1,4‐glucanase gene (Auglu12A) from Aspergillus usamii was successfully expressed in Escherichia coli BL21(DE3). The recombinant enzyme, reAuglu12A was efficiently purified using the one‐step nickel‐nitrilotriacetic acid affinity chromatography. The specific activity of reAuglu12A was 694.8 U/mg, with an optimal temperature of 55°C and pH of 5.0. The reAuglu12A exhibited stability at temperatures up to 60°C and within the pH range of 4.0–5.5. The reAuglu12A hydrolytic activity was increased in the presence of metal ions, especially K+ and Na+, whereas it exhibited a Km and Vmax of 8.35 mg/mL and 1254.02 µmol/min/mg, respectively, toward barley β‐glucan at pH 5.0 and 55°C. The addition of reAuglu12A significantly increased the specific volume (p < 0.05) and reduced crumb firmness and chewiness (p < 0.05) of wheat–barley sourdough bread during a 7‐day storage period compared to the control. Overall, the quality of wheat–barley sourdough bread was improved after incorporation of reAuglu12A (especially at 3000 U/300 g). These changes were attributed to the synergistic effect of acidification by sourdough and its metabolites which provided a conducive environment for the optimal action of reAuglu12A in the degradation of β‐glucans of barley flour in sourdough. This stabilized the dough structure, thereby enhancing the quality, texture, and shelf life of the bread. These findings suggest that reAuglu12A holds promise as a candidate for β‐glucanase application in the baking industry.

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Human placental mesenchymal stem cells regulate inflammation via the NF‑κB signaling pathway

Cited by 6 publications

References 42 publications

Mesenchymal stromal cells and alpha-1 antitrypsin have a strong synergy in modulating inflammation and its resolution

Mesenchymal stromal cells and alpha-1 antitrypsin have a strong synergy in modulating inflammation and its resolution

Mesenchymal stromal cells and alpha-1 antitrypsin have a strong synergy in modulating inflammation and its resolution

Expression and characterization of β‐1,3‐1,4‐glucanase of Aspergillus usamii in Escherichia coli and its application in sourdough bread making

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