scholarly journals EXAMINING LOCALLY EXPRESSED mRNA OF INFLAMMATORY MEDIATOR GENES IN A MODEL OF RETINAL PIGMENT EPITHELIUM ATROPHY AND RETINAL DEGENERATION INDUCED BY SUBRETINAL SALINE INJECTION IN RABBITS

2021 ◽  
Vol 23 (4) ◽  
pp. 813-818
Author(s):  
V. V. Neroev ◽  
N. V. Balatskaya ◽  
E. V. Svetlova ◽  
N. V. Neroeva ◽  
P. A. Ilyukhin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sodium Chloride ◽  
Mrna Expression ◽  
Chloride Solution ◽  
Sodium Chloride Solution ◽  
Cytokine Gene Expression ◽  
Cytokine Gene ◽  
Rpe Atrophy ◽  
New Strategies ◽  
Subretinal Injection

Degenerative-dystrophic retinal diseases, particularly age-related macular degeneration (AMD), are now considered to be the lead cause of blindness and low vision in developed countries, with a steadily increasing trend. Recent publications provide evidence for the involvement of inflammatory mechanisms in TMD development and progression unveiled due to advances in innate and adaptive immunity research. However, the immunopathogenesis of atrophic AMD form, “geographic atrophy” (GA) remains largely unstudied. Objective: to investigate local mRNA expression of inflammatory cytokines IL-1β, IL-18, CCL2/MCP-1 in a model of RPE atrophy induced after subretinal injection of 0.9% sodium chloride solution in experimental rabbits. The investigation was carried out in tissue complex retina-RPE-choroid (TC) samples isolated from eyes of 23 albino New Zealand rabbits after modeling RPE atrophy by subretinal injection of 0.9% sodium chloride solution and 5 healthy rabbits lacking eye lesions. Animals in the experimental group (one week before surgical intervention, in the early period, and in the period of sustained RPE atrophy formation) and controls were subjected to optical coherence tomography (OCT) and ocular fundus autofluorescence (FAF). Evaluation of proinflammatory cytokine gene expression levels in TC was performed by RT-PCR. Results. Subretinal injection of 0.01 ml of 0.9% sodium chloride solution induced experimental RPE atrophy development in rabbits vs. control that was associated with multidirectional changes of IL-1β, IL-18, MCP-1/CCL2 gene mRNA expression. Three types of response in the TC, formed during development of atrophic changes and determined by the value of local cytokine gene expression were characterized: 1) hypo/ no response – decreased/no expression; 2) normal response – moderate increase; 3) hyper response – overexpression. 69.6% of animals with persistent atrophy had a moderate to hypertrophic increase in locally expressed mRNA MCP-1/CCL2, whereas 30% cases had significantly increased IL-1β mRNA expression – factors damaging the blood-retinal barrier and contributing to posterior segment immune privilege. It should be taken into account while developing new strategies for treatment of ophthalmic pathology, in particular the currently actively studied and tested options for RPE stem cell transplantation into subretinal space. The data obtained may be useful to investigate various types of RPE atrophy and develop new strategies of ophthalmopathology treatment in preclinical studies. 

scholarly journals Elevated Glucose and Diabetes Promote Interleukin-12 Cytokine Gene Expression in Mouse Macrophages

Endocrinology ◽  
2006 ◽  
Vol 147 (5) ◽  
pp. 2518-2525 ◽  
Author(s):  
Yeshao Wen ◽  
Jiali Gu ◽  
Shu-Lian Li ◽  
Marpadga A. Reddy ◽  
Rama Natarajan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Spontaneous Diabetes ◽  
Fold Increase ◽  
Cytokine Gene Expression ◽  
Interleukin 12 ◽  
Protein Accumulation ◽  
Cytokine Gene ◽  
Elevated Glucose

Inflammation is emerging as an important mechanism for micro- and macrovascular complication of diabetes. The macrophage plays a key role in the chronic inflammatory response in part by generating particular cytokines. IL-1β, IL-6, IL12, IL-18, TNFα, and interferon-γ are produced primarily in macrophages and have been associated with accelerated atherosclerosis and altered vascular wall function. In this study, we evaluated the effect and mechanism of high glucose (HG) on gene expression of these cytokines in mouse peritoneal macrophages (MPM). HG led to a 2-fold increase in the mRNA expression of these cytokines, with IL-12 showing the highest activation (5.4-fold) in a time-dependent (3–12 h) and dose-dependent (10, 17.5, and 25 mmol/liter) manner. The effects were specific to HG because mannitol and 3-O-methyl-glucose had no effect on cytokine mRNA expression. HG also increased IL-12 protein accumulation from MPM. We also explored the role of induced and spontaneous diabetes on inflammatory cytokine expression in MPM. Increases in expression in MPM of multiple inflammatory cytokines, including a 20-fold increase in IL-12 mRNA, were observed in streptozotocin-induced type 1 diabetic mice as well as type 2 diabetic db/db mice, suggesting that cytokine gene expression is increased by hyperglycemia in vivo. We next explored potential mechanisms of HG-induced increases in IL-12 mRNA. HG increased the activity of protein kinase C, p38 MAPK (p38), c-Jun terminal kinase, and inhibitory-κB kinase in MPM. Furthermore, inhibitors of these signaling pathways significantly reduced HG-induced IL-12 mRNA expression in MPM. These results provide evidence for a potentially important mechanism linking elevated glucose and diabetes to inflammation.

Hyperthermia-enhanced splenic cytokine gene expression is mediated by the sympathetic nervous system

2004 ◽  
Vol 19 (2) ◽  
pp. 175-183 ◽  
Author(s):  
Chanran K. Ganta ◽  
Frank Blecha ◽  
Roman R. Ganta ◽  
Bryan G. Helwig ◽  
Sujatha Parimi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Gene Array ◽  
Cytokine Gene Expression ◽  
Whole Body ◽  
Cytokine Gene ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Nerve Discharge ◽  
Intact Rats

Whole body hyperthermia (WBH) has been used in experimental settings as an adjunct to radiochemotherapy for the treatment of various malignant diseases. The therapeutic effect of WBH has been hypothesized to involve activation of the immune system, although the effect of hyperthermia-induced activation of sympathetic nerve discharge (SND) on splenic immune function is not known. We tested the hypothesis that heating-induced splenic sympathoexcitation would alter splenic cytokine gene expression as determined using gene array and real-time RT-PCR analyses. Experiments were performed in splenic-intact and splenic-denervated anesthetized Sprague-Dawley rats ( n=32). Splenic SND was increased during heating (internal temperature increased from 38° to 41°C) in splenic-intact rats but remained unchanged in nonheated splenic-intact rats. Splenic interleukin-1β (IL-1β), interleukin-6 (IL-6), and growth-regulated oncogene 1 (GRO 1) mRNA expression was higher in heated than in nonheated splenic-intact rats. Splenic IL-1β, IL-6, and GRO 1 mRNA expression was reduced in heated splenic-denervated compared with heated splenic-intact rats, but did not differ between heated splenic-denervated and nonheated splenic-intact rats. These results support the hypothesis that hyperthermia-induced activation of splenic SND enhances splenic cytokine gene expression.

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