Melatonin inhibits Müller cell activation and pro‐inflammatory cytokine production via upregulating the MEG3/miR‐204/Sirt1 axis in experimental diabetic retinopathy

2020 ◽  
Vol 235 (11) ◽  
pp. 8724-8735 ◽  
Author(s):  
Yuanyuan Tu ◽  
Manhui Zhu ◽  
Zhenzhen Wang ◽  
Kun Wang ◽  
Lili Chen ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Inflammatory Cytokine ◽  
Cell Activation ◽  
Cytokine Production ◽  
Müller Cell ◽  
Inflammatory Cytokine Production ◽  
Muller Cell

scholarly journals Mediation of FoxO1 in Activated Neuroglia Deficient for Nucleoside Diphosphate Kinase B during Vascular Degeneration

Neuroglia ◽  
2018 ◽  
Vol 1 (1) ◽  
pp. 280-291 ◽  
Author(s):  
Yi Qiu ◽  
Hongpeng Huang ◽  
Anupriya Chatterjee ◽  
Loïc Teuma ◽  
Fabienne Baumann ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Cell Activation ◽  
Neurovascular Unit ◽  
Nucleoside Diphosphate Kinase ◽  
Müller Cells ◽  
Müller Cell ◽  
Muller Cells ◽  
Nucleoside Diphosphate Kinase B ◽  
Muller Cell ◽  
Underlying Mechanisms

The pathogenesis of diabetic retinopathy is closely associated with the breakdown of the neurovascular unit including the glial cells. Deficiency of nucleoside diphosphate kinase B (NDPK-B) results in retinal vasoregression mimicking diabetic retinopathy. Increased retinal expression of Angiopoietin-2 (Ang-2) initiates vasoregression. In this study, Müller cell activation, glial Ang-2 expression, and the underlying mechanisms were investigated in streptozotocin-induced diabetic NDPK-B deficient (KO) retinas and Müller cells isolated from the NDPK-B KO retinas. Müller cells were activated and Ang-2 expression was predominantly increased in Müller cells in normoglycemic NDPK-B KO retinas, similar to diabetic wild type (WT) retinas. Diabetes induction in the NDPK-B KO mice did not further increase its activation. Additionally, cultured NDPK-B KO Müller cells were more activated and showed higher Ang-2 expression than WT cells. Müller cell activation and Ang-2 elevation were observed upon high glucose treatment in WT, but not in NDPK-B KO cells. Moreover, increased levels of the transcription factor forkhead box protein O1 (FoxO1) were detected in non-diabetic NDPK-B KO Müller cells. The siRNA-mediated knockdown of FoxO1 in NDPK-B deficient cells interfered with Ang-2 upregulation. These data suggest that FoxO1 mediates Ang-2 upregulation induced by NDPK-B deficiency in the Müller cells and thus contributes to the onset of retinal vascular degeneration.

scholarly journals Non-T Cell Activation Linker (NTAL) Negatively Regulates TREM-1/DAP12-Induced Inflammatory Cytokine Production in Myeloid Cells

2007 ◽  
Vol 178 (4) ◽  
pp. 1991-1999 ◽  
Author(s):  
Anja S. Tessarz ◽  
Sandra Weiler ◽  
Kai Zanzinger ◽  
Pavla Angelisová ◽  
Václav Horejsí ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Inflammatory Cytokine ◽  
Cell Activation ◽  
Cytokine Production ◽  
Myeloid Cells ◽  
Inflammatory Cytokine Production

scholarly journals VEGF-Independent Activation of Müller Cells by the Vitreous from Proliferative Diabetic Retinopathy Patients

2021 ◽  
Vol 22 (4) ◽  
pp. 2179
Author(s):  
Sara Rezzola ◽  
Jessica Guerra ◽  
Adwaid Manu Krishna Chandran ◽  
Alessandra Loda ◽  
Anna Cancarini ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Growth Factor ◽  
Proliferative Diabetic Retinopathy ◽  
Cell Activation ◽  
Müller Cells ◽  
Müller Cell ◽  
Muller Cells ◽  
Anti Vegf ◽  
Muller Cell ◽  
The Impact

Proliferative diabetic retinopathy (PDR), a major complication of diabetes mellitus, results from an inflammation-sustained interplay among endothelial cells, neurons, and glia. Even though anti-vascular endothelial growth factor (VEGF) interventions represent the therapeutic option for PDR, they are only partially efficacious. In PDR, Müller cells undergo reactive gliosis, produce inflammatory cytokines/chemokines, and contribute to scar formation and retinal neovascularization. However, the impact of anti-VEGF interventions on Müller cell activation has not been fully elucidated. Here, we show that treatment of MIO-M1 Müller cells with vitreous obtained from PDR patients stimulates cell proliferation and motility, and activates various intracellular signaling pathways. This leads to cytokine/chemokine upregulation, a response that was not mimicked by treatment with recombinant VEGF nor inhibited by the anti-VEGF drug ranibizumab. In contrast, fibroblast growth factor-2 (FGF2) induced a significant overexpression of various cytokines/chemokines in MIO-M1 cells. In addition, the FGF receptor tyrosine kinase inhibitor BGJ398, the pan-FGF trap NSC12, the heparin-binding protein antagonist N-tert-butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe Boc2, and the anti-inflammatory hydrocortisone all inhibited Müller cell activation mediated by PDR vitreous. These findings point to a role for various modulators beside VEGF in Müller cell activation and pave the way to the search for novel therapeutic strategies in PDR.

scholarly journals Myeloid-derived NF-κB negative regulation of PU.1 and c/EBP-β-driven pro-inflammatory cytokine production restrains LPS-induced shock

2016 ◽  
Vol 23 (2) ◽  
pp. 175-187 ◽  
Author(s):  
Simone Vanoni ◽  
Yi-Ting Tsai ◽  
Amanda Waddell ◽  
Lisa Waggoner ◽  
Jared Klarquist ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Cell Activation ◽  
Cytokine Production ◽  
Endotoxic Shock ◽  
Elevated Serum ◽  
Experimental Studies ◽  
Negative Regulation ◽  
Dendritic Cell Activation ◽  
Inflammatory Cytokine Production ◽  
Lps Challenge

Sepsis is a life-threatening event predominantly caused by Gram-negative bacteria. Bacterial infection causes a pronounced macrophage (MΦ) and dendritic cell activation that leads to excessive pro-inflammatory cytokine IL-1β, IL-6 and TNF-α production (cytokine storm), resulting in endotoxic shock. Previous experimental studies have revealed that inhibiting NF-κB signaling ameliorates disease symptoms; however, the contribution of myeloid p65 in endotoxic shock remains elusive. In this study, we demonstrate increased mortality in mice lacking p65 in the myeloid lineage (p65Δmye) compared with wild type mice upon ultra-pure LPS challenge. We show that increased susceptibility to LPS-induced shock was associated with elevated serum level of IL-1β and IL-6. Mechanistic analyses revealed that LPS-induced pro-inflammatory cytokine production was ameliorated in p65-deficient bone marrow-derived MΦs; however, p65-deficient ‘activated’ peritoneal MΦs exhibited elevated IL-1β and IL-6. We show that the elevated pro-inflammatory cytokine secretion was due, in part, to increased accumulation of IL-1β mRNA and protein in activated inflammatory MΦs. The increased IL-1β was linked with heightened binding of PU.1 and CCAAT/enhancer binding protein-β to Il1b and Il6 promoters in activated inflammatory MΦs. Our data provide insight into a role for NF-κB in the negative regulation of pro-inflammatory cytokines in myeloid cells.

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