Protection from Endotoxic Uveitis by Intravitreal Resolvin D1: Involvement of Lymphocytes, miRNAs, Ubiquitin-Proteasome, and M1/M2 Macrophages

This study investigated the protective effects of intravitreal Resolvin D1 (RvD1) against LPS-induced rat endotoxic uveitis (EIU). RvD1 was administered into the right eye at a single injection of 5 μL volume containing 10–100–1000 ng/kg RvD1 1 h post-LPS injection (200 μg,Salmonella minnesota) into thefootpad of Sprague-Dawley rats. 24 h later, the eye was enucleated and examined for clinical, biochemical, and immunohistochemical evaluations. RvD1 significantly and dose-dependently decreased the clinical score attributed to EIU, starting from the dose of 10 ng/kg and further decreased by 100 and 1000 ng/kg. These effects were accompanied by changes in four important determinants of the immune-inflammatory response within the eye: (i) the B and T lymphocytes, (ii) the miRNAs pattern, (iii) the ubiquitin-proteasome system (UPS), and (iv) the M1/M2 macrophage phenotype. LPS+RvD1 treated rats showed reduced presence of B and T lymphocytes and upregulation of miR-200c-3p, miR 203a-3p, miR 29b-3p, and miR 21-5p into the eye compared to the LPS alone. This was paralleled by decreases of the ubiquitin, 20S and 26S proteasome subunits, reduced presence of macrophage M1, and increased presence of macrophage M2 in the ocular tissues. Accordingly, the levels of the cytokine TNF-α, the chemokines MIP1-αand NF-κB were reduced.

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Resolvin D1 Reduces the Immunoinflammatory Response of the Rat Eye following Uveitis

Mediators of Inflammation ◽

10.1155/2012/318621 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 27

Author(s):

Rossi Settimio ◽

Di Filippo Clara ◽

Ferraraccio Franca ◽

Simonelli Francesca ◽

D'Amico Michele

Keyword(s):

T Lymphocytes ◽

Clinical Score ◽

Myeloperoxidase Activity ◽

Sprague Dawley ◽

Resolvin D1 ◽

Sterile Saline ◽

Sprague Dawley Rats ◽

Pmn Leukocytes ◽

Significant Release ◽

Inflammatory Profile

This study investigated whether the administration of resolvin D1 to rats with endotoxininduced uveitis (EIU) ameliorates the immuno-inflammatory profile of the eye. 24 h after the administration of 200 μg LPS into the footpad of Sprague-Dawley rats, severe changes of the structure of the eye occurred concomitantly with a severe inflammatory and immune response. These latter included strong infiltration of PMN leukocytes CD11b+T-lymphocytes CD4+and CD8+within the eye and a significant release of the cytokines/chemokines TNF-alpha, CXCL8, and RANTES too. Bolus of resolvin D1 (RvD1; 10–100–1000 ng/kg in 200 μL of sterile saline via the tail vein) significantly and dose-dependently (i) reduced the development of the ocular derangement caused by LPS; (ii) reduced the clinical score attributed to EIU; (iii) reduced the protein concentration and myeloperoxidase activity (MPO) in aqueous humor (AqH); and (iv) reduced neutrophils, T-lymphocytes, and cytokines within the eye.

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Interplay between Intravitreal RvD1 and Local Endogenous Sirtuin-1 in the Protection from Endotoxin-Induced Uveitis in Rats

Mediators of Inflammation ◽

10.1155/2015/126408 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 6

Author(s):

S. Rossi ◽

C. Di Filippo ◽

C. Gesualdo ◽

F. Testa ◽

M. C. Trotta ◽

...

Keyword(s):

Manganese Superoxide Dismutase ◽

Specific Inhibitor ◽

Sirtuin 1 ◽

Formyl Peptide Receptor ◽

Protective Effects ◽

Sprague Dawley ◽

Resolvin D1 ◽

Manganese Superoxide ◽

Sprague Dawley Rats ◽

Formyl Peptide

Rat endotoxin-induced uveitis (EIU) is a well-established model of human uveitis. In this model, intravitreal injection of resolvin D1 (RvD1, 10–100–1000 ng/kg) 1 hour after subcutaneous treatment of Sprague-Dawley rats with lipopolysaccharide (LPS, 200 μg/rat) significantly prevented the development of uveitis into the eye. RvD1 dose-dependently increased the expression of sirtuin-1 (SIRT1) within the eye, while it decreased the expression of acetyl-p53 and acetyl-FOXO1. These effects were accompanied by local downregulation of some microRNAs related to the expression and activity of SIRT1. These were miR-195-5p, miR-200a-3p, miR-34a-5p, and miR-145-5p. An increase of manganese superoxide dismutase and decrease of caspase 3 were evident after RvD1 treatment. In another set of experiments, the protective effects of RvD1 (1000 ng/kg) were partly abolished by the pretreatment of the rats with EX527 (10 mg/kg/day, i.p.), a specific inhibitor of SIRT1 activity, for 7 days prior to the induction of EIU in rats. Similarly, the effects of RvD1 (1000 ng/kg) on the SIRT1 protein expression were abolished by Boc2,N-t-butoxycarbonyl-PLPLP, a specific formyl-peptide receptor type 2/lipoxin A receptor antagonist. Therefore, an interplay of the SIRT1 activity on the RvD1 mediated resolution of EIU is argued.

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SP400EFFECT OF CHOLECALCIFEROL SUPPLEMENTATION ON TLR7, TLR9, IL-6 AND IFN-Y EXPRESSION IN B AND T LYMPHOCYTES ON CHRONIC DIALYSIS PATIENTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfv193.08 ◽

2015 ◽

Vol 30 (suppl_3) ◽

pp. iii511-iii511

Author(s):

Jose Tarcisio Giffoni de Carvalho ◽

Marion Schneider ◽

Lilian Cuppari ◽

Caren Cristina Grabulosa ◽

Silvia Regina Manfredi ◽

...

Keyword(s):

T Lymphocytes ◽

Chronic Dialysis ◽

Dialysis Patients ◽

Cholecalciferol Supplementation ◽

B And T Lymphocytes

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Bridging autoinflammatory and autoimmune diseases

The Egyptian Journal of Internal Medicine ◽

10.1186/s43162-021-00040-5 ◽

2021 ◽

Vol 33 (1) ◽

Author(s):

Emad M. El-Shebiny ◽

Enas S. Zahran ◽

Sabry A. Shoeib ◽

Eman S. Habib

Keyword(s):

Innate Immunity ◽

T Lymphocytes ◽

Autoimmune Diseases ◽

Adaptive Immunity ◽

High Titre ◽

The Other ◽

Clinical Spectrum ◽

Autoinflammatory Diseases ◽

Main Body ◽

B And T Lymphocytes

Abstract Background Autoimmunity is used to cause by impairment of adaptive immunity alone, whereas autoinflammatory was originally defined as a consequence of unregulated innate immunity. So, the pathogenetic mechanisms of autoimmune diseases were well-thought-out to be mediated by B and T lymphocytes. Whereas, autoinflammatory diseases were defined as unprovoked times of inflammation with the absence of a high titre of autoantibodies. Main body of the abstract Autoimmune and autoinflammatory diseases were split into two groups, but considering the similarities, it can be considered as only one group of diseases with a large immune pathological and clinical spectrum which involves at one end pure autoimmune diseases and the other pure autoinflammatory diseases. Conclusions We can safely conclude that there is bridging between autoinflammatory and autoimmune diseases.

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Knockdown of long non-coding RNA LEF1-AS1 attenuates apoptosis and inflammatory injury of microglia cells following spinal cord injury

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-020-02041-6 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Sheng-Yu Cui ◽

Wei Zhang ◽

Zhi-Ming Cui ◽

Hong Yi ◽

Da-Wei Xu ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Cell Viability ◽

Microglial Cells ◽

Protective Effects ◽

Loss Of Function ◽

Sprague Dawley ◽

Cord Injury ◽

Apoptosis And Inflammation

Abstract Background Spinal cord injury (SCI) is associated with health burden both at personal and societal levels. Recent assessments on the role of lncRNAs in SCI regulation have matured. Therefore, to comprehensively explore the function of lncRNA LEF1-AS1 in SCI, there is an urgent need to understand its occurrence and development. Methods Using in vitro experiments, we used lipopolysaccharide (LPS) to treat and establish the SCI model primarily on microglial cells. Gain- and loss of function assays of LEF1-AS1 and miR-222-5p were conducted. Cell viability and apoptosis of microglial cells were assessed via CCK8 assay and flow cytometry, respectively. Adult Sprague-Dawley (SD) rats were randomly divided into four groups: Control, SCI, sh-NC, and sh-LEF-AS1 groups. ELISA test was used to determine the expression of TNF-α and IL-6, whereas the protein level of apoptotic-related markers (Bcl-2, Bax, and cleaved caspase-3) was assessed using Western blot technique. Results We revealed that LncRNA LEF1-AS1 was distinctly upregulated, whereas miR-222-5p was significantly downregulated in LPS-treated SCI and microglial cells. However, LEF1-AS1 knockdown enhanced cell viability, inhibited apoptosis, as well as inflammation of LPS-mediated microglial cells. On the contrary, miR-222-5p upregulation decreased cell viability, promoted apoptosis, and inflammation of microglial cells. Mechanistically, LEF1-AS1 served as a competitive endogenous RNA (ceRNA) by sponging miR-222-5p, targeting RAMP3. RAMP3 overexpression attenuated LEF1-AS1-mediated protective effects on LPS-mediated microglial cells from apoptosis and inflammation. Conclusion In summary, these findings ascertain that knockdown of LEF1-AS1 impedes SCI progression via the miR-222-5p/RAMP3 axis.

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TNFR2 but not TNFR1 is the main TNFR expressed by B and T lymphocytes in breast cancer draining lymph nodes

Immunology Letters ◽

10.1016/j.imlet.2019.03.013 ◽

2019 ◽

Vol 209 ◽

pp. 36-44 ◽

Cited By ~ 4

Author(s):

Atri Ghods ◽

Abbas Ghaderi ◽

Mahmoud Shariat ◽

Abdol-Rasoul Talei ◽

Fereshteh Mehdipour

Keyword(s):

Breast Cancer ◽

T Lymphocytes ◽

Lymph Nodes ◽

Draining Lymph Nodes ◽

B And T Lymphocytes

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Glia maturation factor-γ regulates murine macrophage iron metabolism and M2 polarization through mitochondrial ROS

Blood Advances ◽

10.1182/bloodadvances.2018026070 ◽

2019 ◽

Vol 3 (8) ◽

pp. 1211-1225 ◽

Cited By ~ 2

Author(s):

Wulin Aerbajinai ◽

Manik C. Ghosh ◽

Jie Liu ◽

Chutima Kumkhaek ◽

Jianqing Zhu ◽

...

Keyword(s):

Iron Metabolism ◽

Mitochondrial Function ◽

Regulatory Protein ◽

M2 Macrophage ◽

Macrophage Phenotype ◽

Glia Maturation Factor ◽

Altered Expression ◽

Murine Macrophages ◽

Cellular Iron ◽

Maturation Factor

Abstract In macrophages, cellular iron metabolism status is tightly integrated with macrophage phenotype and associated with mitochondrial function. However, how molecular events regulate mitochondrial activity to integrate regulation of iron metabolism and macrophage phenotype remains unclear. Here, we explored the important role of the actin-regulatory protein glia maturation factor-γ (GMFG) in the regulation of cellular iron metabolism and macrophage phenotype. We found that GMFG was downregulated in murine macrophages by exposure to iron and hydrogen peroxide. GMFG knockdown altered the expression of iron metabolism proteins and increased iron levels in murine macrophages and concomitantly promoted their polarization toward an anti-inflammatory M2 phenotype. GMFG-knockdown macrophages exhibited moderately increased levels of mitochondrial reactive oxygen species (mtROS), which were accompanied by decreased expression of some mitochondrial respiration chain components, including the iron-sulfur cluster assembly scaffold protein ISCU as well as the antioxidant enzymes SOD1 and SOD2. Importantly, treatment of GMFG-knockdown macrophages with the antioxidant N-acetylcysteine reversed the altered expression of iron metabolism proteins and significantly inhibited the enhanced gene expression of M2 macrophage markers, suggesting that mtROS is mechanistically linked to cellular iron metabolism and macrophage phenotype. Finally, GMFG interacted with the mitochondrial membrane ATPase ATAD3A, suggesting that GMFG knockdown–induced mtROS production might be attributed to alteration of mitochondrial function in macrophages. Our findings suggest that GMFG is an important regulator in cellular iron metabolism and macrophage phenotype and could be a novel therapeutic target for modulating macrophage function in immune and metabolic disorders.

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