scholarly journals MicroRNA-146a Alleviates Experimental Autoimmune Anterior Uveitis in the Eyes of Lewis Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Yung-Ray Hsu ◽  
Shu-Wen Chang ◽  
Yu-Cheng Lin ◽  
Chang-Hao Yang
Keyword(s):  
Dna Binding ◽  
Western Blotting ◽  
Anterior Uveitis ◽  
Binding Activity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Lewis Rats ◽  
Dna Binding Activity ◽  
Clinical Scores ◽  
Experimental Autoimmune Anterior Uveitis ◽  
Experimental Autoimmune

Purpose. This study aimed to determine the effect and roles of microRNA (miRNA, miR) treatment in experimental autoimmune anterior uveitis (EAAU). Materials and Methods. Uveitis was induced in Lewis rats by simultaneous injections of bovine melanin-associated antigen into the hind footpad and the intraperitoneal cavity. The animals were injected intravitreally with low-dose (0.5 μg) or high-dose (1.5 μg) miR-146a. The clinical scores, leukocyte count in the aqueous humor, and histology were assessed. Cytokine changes were evaluated by relative mRNA expression and enzyme-linked immunosorbent assay (ELISA). The expression of nuclear factor kappa B (NF-κB) was assessed by immunofluorescence and Western blotting. Evaluation of the DNA-binding activity of NF-κB was performed by electrophoretic mobility shift assay (EMSA). Results. Treatment with miR-146a significantly attenuated clinical scores and leukocyte infiltration in a dose-dependent manner, a result that was compatible with histological findings. Following miR-146a injections, downregulation of interleukin- (IL-) 1β, IL-6, and IL-12 and interferon- (IFN-) γ and upregulation of IL-10 and IL-17 were noted. The decreased NF-κB expression on immunofluorescence and Western blotting and reduced DNA-binding activity on EMSA were demonstrated following miR-146a treatment. Conclusions. miR-146a effectively reduced intraocular inflammation in EAAU through the inhibition of NF-κB. miR-146a might be a new treatment choice for uveitis.

scholarly journals Expression of MicroRNAs in the Eyes of Lewis Rats with Experimental Autoimmune Anterior Uveitis

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Yung-Ray Hsu ◽  
Shu-Wen Chang ◽  
Yu-Cheng Lin ◽  
Chang-Hao Yang
Keyword(s):  
Anterior Uveitis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dynamic Changes ◽  
Lewis Rats ◽  
Effector Cells ◽  
Cytokine Analysis ◽  
Experimental Autoimmune Anterior Uveitis ◽  
Cytokine Mrnas ◽  
Experimental Autoimmune

Purpose.This study aimed to determine the dynamic changes of NF-κB-related microRNAs (miRNAs) and cytokines over the course of experimental autoimmune anterior uveitis (EAAU) and elucidate the possible immunopathogenesis.Materials and Methods.Uveitis was induced in Lewis rats using bovine melanin-associated antigen. The inflammatory activity of the anterior chamber was clinically scored, and leukocytes in the aqueous humor were quantified. RNA was extracted from the iris/ciliary bodies and popliteal lymph nodes to reveal the dynamic changes of eight target miRNAs (miR-155-5p, miR-146a-5p, miR-182-5p, miR-183-5p, miR-147b, miR-21-5p, miR-9-3p, and miR-223-3p) and six cytokine mRNAs (IFN-γ, IL-17, IL-12A, IL-1β, IL-6, and IL-10).In situhybridization of miRNA and enzyme-linked immunosorbent assay quantification of cytokines were performed to confirm the results.Results. Disease activity and leukocyte quantification were maximum at day 15 after immunization. The profiling of miRNA revealed downregulation of miR-146a-5p, miR-155-5p, miR-223-3p, and miR-147b and upregulation of miR-182-5p, miR-183-5p, and miR-9-3p. Cytokine analysis revealed IFN-γ, IL-17, IL-12A, IL-1β, and IL-6 overexpression, with IL-10 downregulation.Conclusions.Dynamic changes of miRNAs were observed over the course of EAAU. By initiating NF-κB signaling, the expressions of downstream cytokines and effector cells from the Th17 and Th1 lineages were sequentially activated, contributing to the disease.

Expressions of lymphotactin and its receptor, XCR, in Lewis rats with experimental autoimmune anterior uveitis

2010 ◽  
Vol 248 (12) ◽  
pp. 1737-1747 ◽  
Author(s):  
Po-Ting Yeh ◽  
Feng-An Lin ◽  
Chang-Pin Lin ◽  
Chung-May Yang ◽  
Muh-Shy Chen ◽  
...  
Keyword(s):  
Anterior Uveitis ◽  
Lewis Rats ◽  
Experimental Autoimmune Anterior Uveitis ◽  
Experimental Autoimmune

scholarly journals Chitosan Oligosaccharides Attenuate Ocular Inflammation in Rats with Experimental Autoimmune Anterior Uveitis

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
I-Mo Fang ◽  
Chang-Hao Yang ◽  
Chung-May Yang
Keyword(s):  
Inflammatory Mediators ◽  
Anterior Uveitis ◽  
Culture Media ◽  
High Dose ◽  
Dependent Manner ◽  
Protective Effects ◽  
Chitosan Oligosaccharides ◽  
Clinical Scores ◽  
Experimental Autoimmune Anterior Uveitis ◽  
Experimental Autoimmune

We investigated the protective effects and mechanisms of chitosan oligosaccharides (COS) on experimental autoimmune anterior uveitis (EAAU) in rats. EAAU was induced in Lewis rats by footpad and intraperitoneal injections of melanin-associated antigen. The rats received intraperitoneal injections of low-dose (5 mg/kg) or high-dose (10 mg/kg) COS or PBS daily after the immunization. The effects of COS were evaluated by determining the clinical scores and the morphology of the iris/ciliary body (ICB). The expression of inflammatory mediators was evaluated using western blot, immunofluorescence, and ELISA. Treatment with COS significantly attenuated the clinical scores and the leukocyte infiltration in the ICB in a dose-dependent manner. COS effectively reduced the expression of inflammatory mediators (TNF-α, iNOS, MCP-1, RANTES, fractalkine, and ICAM-1). Moreover, COS decreased the IκB degradation and p65 presence in the ICB, which resulted in the inhibition of NF-κB/DNA binding activity. In an in vitro study, sensitized spleen-derived lymphocytes of the COS-treated group showed less chemotaxis toward their aqueous humor and decreased secretion of the above inflammatory mediators in the culture media. COS treated EAAU by inhibiting the activation of NF-κB and reducing the expression of inflammatory mediators. COS might be a potential treatment for acute anterior uveitis.

Expression of chemokine and receptors in Lewis rats with experimental autoimmune anterior uveitis

2004 ◽  
Vol 78 (6) ◽  
pp. 1043-1055 ◽  
Author(s):  
I-Mo Fang ◽  
Chang-Hao Yang ◽  
Chang-Pin Lin ◽  
Chung-May Yang ◽  
Muh-Shy Chen
Keyword(s):  
Anterior Uveitis ◽  
Lewis Rats ◽  
Experimental Autoimmune Anterior Uveitis ◽  
Experimental Autoimmune

scholarly journals Structure of the p53/RNA polymerase II assembly

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Shu-Hao Liou ◽  
Sameer K. Singh ◽  
Robert H. Singer ◽  
Robert A. Coleman ◽  
Wei-Li Liu
Keyword(s):  
Dna Binding ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Conformational Changes ◽  
P53 Protein ◽  
Binding Activity ◽  
Transactivation Domain ◽  
Pol Ii ◽  
Dna Binding Activity ◽  
Regulated Gene Expression

AbstractThe tumor suppressor p53 protein activates expression of a vast gene network in response to stress stimuli for cellular integrity. The molecular mechanism underlying how p53 targets RNA polymerase II (Pol II) to regulate transcription remains unclear. To elucidate the p53/Pol II interaction, we have determined a 4.6 Å resolution structure of the human p53/Pol II assembly via single particle cryo-electron microscopy. Our structure reveals that p53’s DNA binding domain targets the upstream DNA binding site within Pol II. This association introduces conformational changes of the Pol II clamp into a further-closed state. A cavity was identified between p53 and Pol II that could possibly host DNA. The transactivation domain of p53 binds the surface of Pol II’s jaw that contacts downstream DNA. These findings suggest that p53’s functional domains directly regulate DNA binding activity of Pol II to mediate transcription, thereby providing insights into p53-regulated gene expression.

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