scholarly journals High Induction of IL-6 Secretion From hUCMSCs Optimize the Potential of hUCMSCs and TCZ as Therapy for COVID-19-Related ARDS

2021 ◽  
Vol 30 ◽  
pp. 096368972110544
Author(s):  
Huei-Yu Lo ◽  
Shun-Ping Cheng ◽  
Jing-Long Huang ◽  
Kuo-Ting Chang ◽  
Yu-Lung Chang ◽  
...  

Biological and cellular interleukin-6 (IL-6)-related therapies have been used to treat severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure, which prompted further exploration of the role of IL-6 in human umbilical cord mesenchymal stem cell (hUCMSC) therapy. Peripheral blood mononuclear cells (PBMCs) were responders cocultured with hUCMSCs or exogenous IL-6. A PBMC suppression assay was used to analyze the anti-inflammatory effects via MTT assay. The IL-6 concentration in the supernatant was measured using ELISA. The correlation between the anti-inflammatory effect of hUCMSCs and IL-6 levels and the relevant roles of IL-6 and IL-6 mRNA expression was analyzed using the MetaCore functional network constructed from gene microarray data. The location of IL-6 and IL-6 receptor (IL-6R) expression was further evaluated. We reported that hUCMSCs did not initially exert any inhibitory effect on PHA-stimulated proliferation; however, a potent inhibitory effect on PHA-stimulated proliferation was observed, and the IL-6 concentration reached approximately 1000 ng/mL after 72 hours. Exogenous 1000 ng/mL IL-6 inhibited PHA-stimulated inflammation but less so than hUCMSCs. The inhibitory effects of hUCMSCs on PHA-stimulated PBMCs disappeared after adding an IL-6 neutralizing antibody or pretreatment with tocilizumab (TCZ), an IL-6R antagonist. hUCMSCs exert excellent anti-inflammatory effects by inducing higher IL-6 levels, which is different from TCZ. High concentration of IL-6 cytokine secretion plays an important role in the anti-inflammatory effect of hUCMSC therapy. Initial hUCMSC therapy, followed by TCZ, seems to optimize the therapeutic potential to treat COVID-19-related acute respiratory distress syndrome (ARDS).

2021 ◽  
Author(s):  
Huei-Yu Lo ◽  
Shun-Ping Cheng ◽  
Jing-Long Huang ◽  
Kuo-Ting Chang ◽  
Yu-Lung Chang ◽  
...  

Abstract BACKGROUND The biologic and cellular IL-6-related therapies have been used to treat the autoimmune diseases (AID), which prompting us to furtherly explore the IL-6 role in human umbilical cord mesenchymal stem cells (hUCMSCs) therapy.MATERIALS & METHODS Peripheral blood mononuclear cells (PBMCs) were responder co-cultured with hUCMSCs or exogenous IL-6. PBMC suppression assay was used to analyze the anti-inflammatory effects by using the MTT assay. The IL-6 concentration in supernatant was measured using ELISA. The correlation between anti-inflammation effect of hUCMSCs and IL-6 levels, and the relevant roles of IL-6, IL-6 mRNA expression was analyzed using the MetaCore functional network constructed from gene microarray data. The location of IL-6 and IL-6 receptor (IL-6R) expression was furtherly evaluated.RESULTS Initially, hUCMSCs did not exert any inhibitory effect on PBMCs, however, a potent inhibitory effect on PBMCs was observed and the IL-6 concentration reached about 1000 ng/mL after 72 hours. Exogenous 1000 ng/mL IL-6 could inhibit PBMCs inflammations but less than that of hUCMSCs. The hUCMSCs exerts excellent anti-inflammation effect by inducing higher IL-6 level which is different from TCZ IL-6 antagonistCONCLUSIONS High concentration IL-6 cytokine secretion plays an important role in the anti-inflammation effect of hUCMSCs cell therapy.


2020 ◽  
Vol 16 ◽  
Author(s):  
Niloofar Ghorbani ◽  
Maryam Sahebari ◽  
Mahmoud Mahmoudi ◽  
Maryam Rastin ◽  
Shahrzad Zamani ◽  
...  

Objective: Rheumatoid arthritis (RA) is the most prevalent autoimmune arthritis. Berberine is an alkaloid isolated from Berberis vulgaris and its anti-inflammatory effect has been identified. Method: Twenty newly diagnosed RA patients and 20 healthy controls participated. Peripheral mononuclear cells were prepared and stimulated with bacterial lipopolysachharide (LPS,1 µg/ml), exposed to different concentrations of berberine (10 and 50µM) and dexamethasone (10-7 M) as a reference. Toxicity of compounds was evaluated by WST-1 assay. Expression of TNF-α and IL-1β were determined by quantitative real-time PCR. Protein level of secreted TNF-α and IL1β were measured by using ELISA. Result: Berberine did not have any toxic effect on cells, whereas Lipopolysachharide (LPS) stimulation caused a noticeable rise in TNF-α and IL-1β production. Berberine markedly downregulated the expression of both TNF-α and IL1β and inhibits TNF-α and IL-1β secretion from LPS-stimulated PBMCs. Discussion: This study provided molecular basis for anti-inflammatory effect of berberine on human mononuclear cells through the suppression of TNF-a and IL-1secretion. Our findings highlighted the significant inhibitory effect of berberine on proinflammatory responses of mononuclear cells from rheumatoid arthritis individuals, which may be responsible for antiinflammatory property of Barberry. We observed that berberine at high concentration exhibited anti-inflammatory effect in PBMCs of both healthy and patient groups by suppression of TNF-a and IL-1cytokines at both mRNA and protein levels. Conclusions: Berberine may inhibit the gene expression and production of pro-inflammatory cytokines by mononuclear cells in rheumatoid arthritis and healthy individuals without affecting cells viability. Future studies with larger sample size is needed to prove the idea.


PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241080
Author(s):  
Jooyeon Jhun ◽  
Jeonghyeon Moon ◽  
Jaeyoon Ryu ◽  
Yonghee Shin ◽  
Seangyoun Lee ◽  
...  

Coenzyme Q10 (CoQ10), also known as ubiquinone, is a fat-soluble antioxidant. Although CoQ10 has not been approved as medication by the Food and Drug Administration, it is widely used in dietary supplements. Some studies have shown that CoQ10 has anti-inflammatory effects on various autoimmune disorders. In this study, we investigated the anti-inflammatory effects of liposome/gold hybrid nanoparticles encoded with CoQ10 (LGNP-CoQ10). Both CoQ10 and LGNP-CoQ10 were administered orally to mice with collagen-induced arthritis (CIA) for 10 weeks. The inflammation pathology of joint tissues of CIA mice was then analyzed using hematoxylin and eosin and Safranin O staining, as well as immunohistochemistry analysis. We obtained immunofluorescence staining images of spleen tissues using confocal microscopy. We found that pro-inflammatory cytokines were significantly decreased in LGNP-CoQ10 injected mice. Th17 cell and phosphorylated STAT3-expressed cell populations were also decreased in LGNP-CoQ10 injected mice. When human peripheral blood mononuclear cells (PBMCs) were treated with CoQ10 and LGNP-CoQ10, the IL-17 expression of PBMCs in the LGNP-CoQ10-treated group was significantly reduced. Together, these results suggest that LGNP-CoQ10 has therapeutic potential for the treatment of rheumatoid arthritis.


Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 476
Author(s):  
Walied Alarif ◽  
Sultan Al-Lihaibi ◽  
Nahed Bawakid ◽  
Ahmed Abdel-Lateff ◽  
Hamdan Al-malky

Three new rare C12 acetogenins (enyne derivatives 1–3) were isolated from the organic extract obtained from the red alga Laurencia obtusa, collected from the Red Sea. The chemical structures of the isolated compounds were established by spectroscopical data analyses. Potent anti-inflammatory effect of the isolated metabolites was evidenced by inhibition of the release of inflammatory mediators (e.g., TNF-α, IL-1β and IL-6) by employing Human Peripheral Blood Mononuclear Cells (PBMC).


Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6900
Author(s):  
Damariz Marín-Palma ◽  
Jorge H. Tabares-Guevara ◽  
María I. Zapata-Cardona ◽  
Lizdany Flórez-Álvarez ◽  
Lina M. Yepes ◽  
...  

Due to the scarcity of therapeutic approaches for COVID-19, we investigated the antiviral and anti-inflammatory properties of curcumin against SARS-CoV-2 using in vitro models. The cytotoxicity of curcumin was evaluated using MTT assay in Vero E6 cells. The antiviral activity of this compound against SARS-CoV-2 was evaluated using four treatment strategies (i. pre–post infection treatment, ii. co-treatment, iii. pre-infection, and iv. post-infection). The D614G strain and Delta variant of SARS-CoV-2 were used, and the viral titer was quantified by plaque assay. The anti-inflammatory effect was evaluated in peripheral blood mononuclear cells (PBMCs) using qPCR and ELISA. By pre–post infection treatment, Curcumin (10 µg/mL) exhibited antiviral effect of 99% and 99.8% against DG614 strain and Delta variant, respectively. Curcumin also inhibited D614G strain by pre-infection and post-infection treatment. In addition, curcumin showed a virucidal effect against D614G strain and Delta variant. Finally, the pro-inflammatory cytokines (IL-1β, IL-6, and IL-8) released by PBMCs triggered by SARS-CoV-2 were decreased after treatment with curcumin. Our results suggest that curcumin affects the SARS-CoV-2 replicative cycle and exhibits virucidal effect with a variant/strain independent antiviral effect and immune-modulatory properties. This is the first study that showed a combined (antiviral/anti-inflammatory) effect of curcumin during SARS-CoV-2 infection. However, additional studies are required to define its use as a treatment for the COVID-19.


2020 ◽  
Vol 31 ◽  
pp. 101747
Author(s):  
Ampika Phutim-Mangkhalthon ◽  
Aroon Teerakapong ◽  
Patcharaporn Tippayawat ◽  
Noppawan Phumala Morales ◽  
Supawich Morkmued ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Jingying Sai ◽  
Lingxin Xiong ◽  
Jingtong Zheng ◽  
Chuangui Liu ◽  
Yanjiao Lu ◽  
...  

Yinhua Miyanling Tablet (YMT), the Chinese formula, has long been administrated in clinical practice for the treatment of acute pyelonephritis and acute urocystitis. In the current study, we aimed to investigate the anti-inflammatory effect of YMTin vitroand to evaluate the association between anti-inflammation and innate immune response. Human peripheral blood mononuclear cells (PBMCs) were isolated using Ficoll density gradient centrifugation and then were stimulated by Lipopolysaccharide (LPS). The differential gene expression of inflammation-related genes after drug administration was assessed using PCR array, and the protein levels of differential genes were measured by ELISA and Western blot. The result showed that YMT significantly inhibited the expression of NLRP3, Caspase-1, and the downstream cytokine IL-1βand suppressed the production of inflammatory mediators TNF-α, IL-6, IL-10, and MCP-1 in a dose-dependent manner compared to the LPS groupP<0.01. The finding indicated that YMT exhibited anti-inflammatory effectin vitroby suppressing the NLRP3/Caspase-1 inflammasome, and that may have therapeutic potential for the treatment of inflammatory diseases.


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