scholarly journals Mechanisms of immunomodulation and cytoprotection conferred to pancreatic islet by human amniotic epithelial cells

2021 ◽  
Author(s):  
Fanny Lebreton ◽  
Charles H. Wassmer ◽  
Kevin Bellofatto ◽  
Lisa Perez ◽  
Véronique Othenin-Girard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Amniotic Epithelial Cells ◽  
Ifn Γ ◽  
Human Amniotic Epithelial Cells ◽  
Anti Inflammatory ◽  
Islet Transplants ◽  
Pro Inflammatory Cytokines

Abstract Inhibiting pro-inflammatory cytokine activity can reverse inflammation mediated dysfunction of islet grafts. Human amniotic epithelial cells (hAECs) possess regenerative, immunomodulatory and anti-inflammatory properties. We hypothesized that hAECs could protect islets from cellular damage induced by pro-inflammatory cytokines. To verify our hypothesis hAECs monocultures, rat islets (RI), or RI-hAEC co-cultures where exposed to a pro-inflammatory cytokine cocktail (Interferon γ: IFN-γ, Tumor necrosis factor α: TNF-α and Interleukin-1β: IL-1β). The secretion of anti-inflammatory cytokines and gene expression changes in hAECs and viability and function of RI were evaluated. The expression of non-classical Major Histocompatibility Complex (MHC) class I molecules by hAECs cultured with various IFN-γ concentrations were assessed. Exposure to the pro-inflammatory cocktail significantly increased the secretion of the anti-inflammatory cytokines IL6, IL10 and G-CSF by hAECs, which was confirmed by upregulation of IL6, and IL10 gene expression. HLA-G, HLA-E and PDL-1 gene expression was also increased. This correlated with an upregulation of STAT1, STAT3 and NF-κB1gene expression levels. RI co-cultured with hAECs maintained normal function after cytokine exposure compared to RI cultured alone, and showed significantly lower apoptosis rate. Our results show that exposure to pro-inflammatory cytokines stimulates secretion of anti-inflammatory and immunomodulatory factors by hAECs through the JAK1/2 – STAT1/3 and the NF-κB1 pathways, which in turn protects islets against inflammation-induced damages. Integrating hAECs in islet transplants appears as a valuable strategy to achieve to inhibit inflammation mediated islet damage, prolong islet survival, improve their engraftment and achieve local immune protection allowing to reduce systemic immunosuppressive regimens.

scholarly journals Mechanisms of Immunomodulation and Cytoprotection Conferred to Pancreatic Islet by Human Amniotic Epithelial Cells

2021 ◽  
Author(s):  
Fanny Lebreton ◽  
Charles H. Wassmer ◽  
Kevin Bellofatto ◽  
Lisa Perez ◽  
Véronique Othenin-Girard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Amniotic Epithelial Cells ◽  
Ifn Γ ◽  
Human Amniotic Epithelial Cells ◽  
Anti Inflammatory ◽  
Islet Transplants ◽  
Pro Inflammatory Cytokines

Abstract Inhibiting pro-inflammatory cytokine activity can reverse inflammation mediated dysfunction of islet grafts. Human amniotic epithelial cells (hAECs) possess regenerative, immunomodulatory and anti-inflammatory properties. We hypothesized that hAECs could protect islets from cellular damage induced by pro-inflammatory cytokines. To verify our hypothesis hAECs monocultures, rat islets (RI), or RI-hAEC co-cultures where exposed to a pro-inflammatory cytokine cocktail (Interferon γ: IFN-γ, Tumor necrosis factor α: TNF-α and Interleukin-1β: IL-1β). The secretion of anti-inflammatory cytokines and gene expression changes in hAECs and viability and function of RI were evaluated. The expression of non-classical Major Histocompatibility Complex (MHC) class I molecules by hAECs cultured with various IFN-γ concentrations were assessed. Exposure to the pro-inflammatory cocktail significantly increased the secretion of the anti-inflammatory cytokines IL6, IL10 and G-CSF by hAECs, which was confirmed by upregulation of IL6, and IL10 gene expression. HLA-G, HLA-E and PDL-1 gene expression was also increased. This correlated with an upregulation of STAT1, STAT3 and NF-κB1gene expression levels. RI co-cultured with hAECs maintained normal function after cytokine exposure compared to RI cultured alone, and showed significantly lower apoptosis rate. Our results show that exposure to pro-inflammatory cytokines stimulates secretion of anti-inflammatory and immunomodulatory factors by hAECs through the JAK1/2 – STAT1/3 and the NF-κB1 pathways, which in turn protects islets against inflammation-induced damages. Integrating hAECs in islet transplants appears as a valuable strategy to achieve to inhibit inflammation mediated islet damage, prolong islet survival, improve their engraftment and achieve local immune protection allowing to reduce systemic immunosuppressive regimens.

scholarly journals Mechanisms of Immunomodulation and Cytoprotection Conferred to Pancreatic Islet by Human Amniotic Epithelial Cells

2021 ◽  
Author(s):  
Fanny Lebreton ◽  
Reine Hanna ◽  
Charles H. Wassmer ◽  
Kevin Bellofatto ◽  
Lisa Perez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Immune Protection ◽  
Ifn Γ ◽  
Human Amniotic Epithelial Cells ◽  
Anti Inflammatory ◽  
Islet Transplants ◽  
Islet Survival ◽  
Pro Inflammatory Cytokines

AbstractInhibiting pro-inflammatory cytokine activity can reverse inflammation mediated dysfunction of islet grafts. Human amniotic epithelial cells (hAECs) possess regenerative, immunomodulatory and anti-inflammatory properties. We hypothesized that hAECs could protect islets from cellular damage induced by pro-inflammatory cytokines. To verify our hypothesis, hAEC monocultures, rat islets (RI), or RI-hAEC co-cultures where exposed to a pro-inflammatory cytokine cocktail (Interferon γ: IFN-γ, Tumor necrosis factor α: TNF-α and Interleukin-1β: IL-1β). The secretion of anti-inflammatory cytokines and gene expression changes in hAECs and viability and function of RI were evaluated. The expression of non-classical Major Histocompatibility Complex (MHC) class I molecules by hAECs cultured with various IFN-γ concentrations were assessed. Exposure to the pro-inflammatory cocktail significantly increased the secretion of the anti-inflammatory cytokines IL6, IL10 and G-CSF by hAECs, which was confirmed by upregulation of IL6, and IL10 gene expression. HLA-G, HLA-E and PDL-1 gene expression was also increased. This correlated with an upregulation of STAT1, STAT3 and NF-κB1gene expression levels. RI co-cultured with hAECs maintained normal function after cytokine exposure compared to RI cultured alone, and showed significantly lower apoptosis rate. Our results show that exposure to pro-inflammatory cytokines stimulates secretion of anti-inflammatory and immunomodulatory factors by hAECs through the JAK1/2 – STAT1/3 and the NF-κB1 pathways, which in turn protects islets against inflammation-induced damages. Integrating hAECs in islet transplants appears as a valuable strategy to achieve to inhibit inflammation mediated islet damage, prolong islet survival, improve their engraftment and achieve local immune protection allowing reducing systemic immunosuppressive regimens. Graphical Abstract This study focuses on the cytoprotective effect of isolated hAECs on islets exposed to pro-inflammatory cytokines in vitro. Exposure to pro-inflammatory cytokines stimulated secretion of anti-inflammatory and immunomodulatory factors by hAECs putatively through the JAK1/2 – STAT1/3 and the NF-κB1 pathways. This had protective effect on islets against inflammation-induced damages. Taken together our results indicate that incorporating hAECs in islet transplants could be a valuable strategy to inhibit inflammation mediated islet damage, prolong islet survival, improve their engraftment and achieve local immune protection allowing to reduce systemic immunosuppressive regimens.

scholarly journals Camel milk Whey Inhibits Inflammatory Colorectal Cancer Development Via Down regulation of Pro-inflammatory Cytokines in Induced AOM/DSS Mouse Model

2019 ◽  
pp. 256 ◽  
Author(s):  
Mariam M. Al-Omari ◽  
Razan B. Al-Ghariebeh, Abed Alkarem Abu Alhaija ◽  
Heba Al- Zoubi ◽  
Khaled M. Al-Qaoud
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Camel Milk ◽  
Cytokine Gene Expression ◽  
Milk Whey ◽  
Potential Activity ◽  
Ifn Γ ◽  
Anti Inflammatory

Camel milk (CM) has got an increasing interest by traditional healers and medical practitioners in areas where camels are raised for their therapeutic potential. To investigate the potential activity of CM against cancer on scientific bases, azoxymethane (AOM)/Dextran Sodium Sulfate (DSS) colitis Balb/c mouse model of CRC was used and CM whey was given orally during disease development. Colitis associated symptoms and tumor development were followed during the experiment and at the day of termination. Pro-inflammatory and anti-inflammatory cytokine gene expression were quantified using qPCR. The results showed a significant effect for CM whey on the reduction of early stage development of CRC and colon inflammation symptoms, as revealed by enhanced weight gain, reduced bloody stool and diarrhea. A concurrent reduction in gene expression of the inflammatory cytokine IL-6 was evident in colon tissue of CM whey treated mice. Moreover, both IFN-γ and IL-8 gene expression was also significantly reduced in treated mice. On the contrary, the expression of anti-inflammatory cytokines IL-10 was elevated in colon tissues of CM treated mice. In addition, iNOS, a marker for inflamed mucosa was down-regulated in treated mice. A control bovine milk whey treated group showed similar effect on IL-8, IL-6 and iNOS gene expression, whereas an elevation in IFN-γ was noticed in this group. Our results indicate the potential activity of CM whey in reducing the development of CRC in mice mainly by reducing colitis induction by chemical stimuli. Whether the active substance responsible for this activity is single or combined deserves further investigation.

scholarly journals P0527AROLE OF PROMOTING INFLAMMATION OF KLF6 IN ACUTE KIDNEY INURY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Dan Li ◽  
Chenyu Li ◽  
Yan Xu
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Tnf Α ◽  
Public Dataset ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine ◽  
Pro Inflammatory Cytokines

Abstract Background and Aims Acute kidney injury (AKI), commonly appeared in cardiac arrest, surgery and kidney transplantation which involved in ischemia-reperfusion (IR) injury of kidney. However, the mechanisms underlying inflammatory response in IR AKI is still unclear. Method Public dataset showed kruppel-like factor 6 (KLF6) was significantly highly expressed (P<0.05) in AKI, implies KLF6 might be associated with AKI. To evaluate the mechanism of KLF6 on IR AKI, 30 rats were randomly divided into sham and IR group, and were sacrificed at 0 h, 3 h, 6 h, 12 h or 24 h after IR. Results The results showed KLF6 expression was peaking at 6 h after IR, and the expression of pro-inflammatory cytokines MCP-1 and TNF-α were increased both in serum and kidney tissues after IR, while anti-inflammatory cytokine IL-10 was decreased after IR. Furthermore, in vitro results showed KLF6 knock-down reduced the pro-inflammatory cytokines expression and increased the anti-inflammatory cytokines expression. Conclusion These results suggest that (1) KLF6 might be a novel biomarker for early diagnosis of AKI and (2) targeting KLF6 expression may offer novel strategies to protect kidneys from IR AKI Figure KLF6, AKI, Control Inflammation

scholarly journals Extracellular vesicles from human cardiovascular progenitors trigger a reparative immune response in infarcted hearts

2020 ◽  
Author(s):  
Bruna Lima Correa ◽  
Nadia El Harane ◽  
Ingrid Gomez ◽  
Hocine Rachid Hocine ◽  
José Vilar ◽  
...  
Keyword(s):  
Immune Response ◽  
Extracellular Vesicles ◽  
Inflammatory Cytokines ◽  
Nk Cell ◽  
Inflammatory Monocytes ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Abstract Aims The cardioprotective effects of human induced pluripotent stem cell-derived cardiovascular progenitor cells (CPC) are largely mediated by the paracrine release of extracellular vesicles (EV). We aimed to assess the immunological behaviour of EV-CPC, which is a prerequisite for their clinical translation. Methods and results Flow cytometry demonstrated that EV-CPC expressed very low levels of immune relevant molecules including HLA Class I, CD80, CD274 (PD-L1), and CD275 (ICOS-L); and moderate levels of ligands of the natural killer (NK) cell activating receptor, NKG2D. In mixed lymphocyte reactions, EV-CPC neither induced nor modulated adaptive allogeneic T cell immune responses. They also failed to induce NK cell degranulation, even at high concentrations. These in vitro effects were confirmed in vivo as repeated injections of EV-CPC did not stimulate production of immunoglobulins or affect the interferon (IFN)-γ responses from primed splenocytes. In a mouse model of chronic heart failure, intra-myocardial injections of EV-CPC, 3 weeks after myocardial infarction, decreased both the number of cardiac pro-inflammatory Ly6Chigh monocytes and circulating levels of pro-inflammatory cytokines (IL-1α, TNF-α, and IFN-γ). In a model of acute infarction, direct cardiac injection of EV-CPC 2 days after infarction reduced pro-inflammatory macrophages, Ly6Chigh monocytes, and neutrophils in heart tissue as compared to controls. EV-CPC also reduced levels of pro-inflammatory cytokines IL-1α, IL-2, and IL-6, and increased levels of the anti-inflammatory cytokine IL-10. These effects on human macrophages and monocytes were reproduced in vitro; EV-CPC reduced the number of pro-inflammatory monocytes and M1 macrophages, while increasing the number of anti-inflammatory M2 macrophages. Conclusions EV-CPC do not trigger an immune response either in in vitro human allogeneic models or in immunocompetent animal models. The capacity for orienting the response of monocyte/macrophages towards resolution of inflammation strengthens the clinical attractiveness of EV-CPC as an acellular therapy for cardiac repair.

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