초록 ▼

이번 연구는 실험적 자가면역 포도막염에서 시스티아민의 항염증 작용에 대하여 알아보았다. 시스티아민의 항염증 작용을 임상적, 병리학적 관점, TG 활성도 및 Th1/Th17 사이토카인의 발현으로 알아보고, 항염증 효과가 임상적, 병리학적 호전과 일치하는지 알아보았다.
1. 포도막염 유발 13일, 21일에서 관찰한 포도막염의 임상적 분석에서 시스티아민 투여군이 대조군(vehicle 투여군)에 비해 염증세포의 침윤이 현저히 적었다.
2. 시스티아민 투여군 (14.6일) 이 대조군 (vehicle 투여군, 12.1일)에 비하여

이번 연구는 실험적 자가면역 포도막염에서 시스티아민의 항염증 작용에 대하여 알아보았다. 시스티아민의 항염증 작용을 임상적, 병리학적 관점, TG 활성도 및 Th1/Th17 사이토카인의 발현으로 알아보고, 항염증 효과가 임상적, 병리학적 호전과 일치하는지 알아보았다.
1. 포도막염 유발 13일, 21일에서 관찰한 포도막염의 임상적 분석에서 시스티아민 투여군이 대조군(vehicle 투여군)에 비해 염증세포의 침윤이 현저히 적었다.
2. 시스티아민 투여군 (14.6일) 이 대조군 (vehicle 투여군, 12.1일)에 비하여 포도막염 발생이 유의하게 지연되었다 (p=0.02, Mann-Whitney test).
3. 시스티아민 투여군이 대조군에 비하여 염증세포의 침윤, TG 활성도, Th1/Th17 사이토카인 발현이 적었다.
이상의 결과로 시스티아민이 실험적 자가면역 포도막염 동물모델에서 항염증 효과가 있으며, 이는 Th1/Th17 사이토카인 발현 억제 때문일 가능성이 있다. 따라서 내인성 포도막염에서 시스티아민이 새로운 치료제로 사용될 가능성이 있음을 알 수 있었다.

Abstract ▼

1. Background
Endogenous uveitis is an intraocular inflammatory disease, which can lead to binocular blindness in 10% of cases.
The pathogenesis of endogenous uveitis still remains unclear,
although a CD4+ T cell-mediated autoimmune response plays a crucial role in various subtypes of the u

1. Background
Endogenous uveitis is an intraocular inflammatory disease, which can lead to binocular blindness in 10% of cases.
The pathogenesis of endogenous uveitis still remains unclear,
although a CD4+ T cell-mediated autoimmune response plays a crucial role in various subtypes of the uveitis.
Experimental autoimmune uveitis (EAU) is an animal model for several posterior segment intraocular inflammations in human.
Transglutaminase (TG) is a multifunctional, ubiquitous protein found in most mammalian tissues capable of enzymatic, cell adhesion, cell signaling, and G-protein activities. The activity of TG is of interest because it is believed to be involved in the pathogenesis of diseases such as celiac sprue, type 2 diabetes, rheumatoid arthritis, liver cirrhosis, pulmonary and renal fibrosis.
In the present study, we investigated the effect of cysteamine on EAU in mouse. The potential for reducing the TG activity suggests that cysteamine provides therapeutic advantage in acute and chronic inflammatory conditions in which activation of TG plays a major role. To the best of our knowledge, there have been no reports on the effect of cysteamine on intraocular inflammation.
II. Materials and Methods
EAU was induced in female C57BL/6 wild-type mice by a footpad injection of human IRBP1-20 (250ug/mouse) emulsified in incomplete Freud adjuvant (IFA) containing 2.5mg/ml M. tuberculosis.
From one day before the IRBP inoculation, cysteamine, TG inhibitor (20mg/kg, 40mg/kg) was daily administered by intraperitoneal injection. Control group received the same amount of vehicle only.
After 1 week, the draining lymph nodes were collected, and T lymphocytes were analyzed for cytokine assay by intracellular staining. In addition, clinical, histopathology, and TG activity were analyzed.
III. Results
A single immunization of IRBP peptide led to cellular infiltrates and significant structural damage of the retina. Disease onset was significantly delayed in cysteamine-treated mice (14.6 days) compared to untreated mice (12.1 days, p=0.02). The number of inflammatory cells, the TG activity, and the levels of Th1 and Th17-type cytokines in the groups treated with cysteamine were significantly decreased. TG2 Knock-out mouse have increased number of inflammatory cell compared to control group, but there was no difference between the two groups.
IV. Conclusions
The results suggest that cysteamine has an anti-inflammatory effect that is due to the blocking of the expression of Th1 and Th17 cytokines. This finding demonstrated the therapeutic potential of cysteamine for the control of endogenous ocular inflammatory diseases.