미세먼지 노출이 안구조직과 경부림프절에서 NLRP3 인플라마좀 발현에 미치는 효과

• Published in: Daihan angwa haghoi jabji Vol. 59; no. 2; pp. 130 - 136
• Main Author: 강수연(Su-Yeon Kang), 강보람(Boram Kang), 김효명(Hyo Myung Kim), 송종석(Jong-Suk Song)
• Format: Journal Article
• Language: Korean
• Published: 대한안과학회 01.02.2018
• Subjects: 안과학; IL-1β; NLRP3 inflammasome; Dry eye; Particulate matter
• ISSN: 0378-6471; 2092-9374

목적: 안구표면이 미세먼지에 노출되었을 때 안구조직과 경부 림프절에서 nucleotide-binding domain leucine-rich repeats, pyrindomain-containing 3 (NLRP3) 인플라마좀 복합체와 주요 염증 사이토카인인 interleukin (IL)-1β의 발현이 어떻게 변화하는지 알아보고자 하였다. 대상과 방법: 5주된 Sprague-Dawley 수컷 쥐(무게, 250-300g)를 대상으로 하였다. 쥐는 무작위로 공기 중에서 티타늄디옥사이드 마이크로입자에 노출시킨 실험군(n=12)과 정상 대조군(n=12)으로 나누어 진행하였다. 티타늄디옥사이드 마이크로입자에 의해 지름 10마이크로미터 이하의 미세먼지 농도(particulate matter [PM] 10)가 평균 331 ± 83 μg/m3가 되는 환경에서 쥐를 하루 2시간씩 2회, 5일간 노출시켰다. 안구표면의 손상을 평가하기 위해 각막형광염색을 시행하였고, 염증반응이 국소 림프절에 전달되는지 평가하기 위해 경부림프절 크기를 측정하였으며 각결막 조직과 경부림프절에서 NLRP3 인플라마좀 복합체의 발현을 정량적으로 평가하였다. 결과: 티타늄디옥사이드 마이크로입자에 노출시킨 실험군에서 대조군에 비해 각막형광염색점수가 유의하게 증가하였고(p=0.002) 경부 림프절의 크기도 증가하였다(p=0.004). 각결막 조직과 경부림프절에서 NLRP3 신호전달체계에 관여하는 NLRP3와 apoptosisassociated speck-like protein containing a caspase activation and recruitment domain (CARD) domain (ASC)의 발현은 대조군에 비해 유의하게 증가하였으며(각각, p=0.037), caspase-1과 IL-1β의 경우 불활성 상태인 전구체의 양은 감소하였으나 활성화 형태의 발현은 대조군에 비해 유의하게 증가하였다(각각, p=0.037). 결론: 안구표면이 미세먼지에 노출되었을 때 NLRP3 인플라마좀 복합체 신호전달체계가 활성화되어 염증 사이토카인인 IL-1β의 생성이 증가하였으며 이러한 기전이 미세먼지에 의한 안구표면 염증반응에 관여하는 것으로 판단된다. Purpose: To evaluate changes of the NLRP3 inflammasome complex and proinflammatory cytokine interleukin (IL)-1β in ocular tissues and cervical lymph nodes when the ocular surface was exposed to particulate matter. Methods: Five-week-old Sprague Dawley male rats, each weighing 250–300 g, were used in this study. The rats were randomly divided into two groups involving the TiO2-exposed group (n = 12) and control group (n = 12). Rats in the TiO2-exposed group were exposed to airborne TiO2 microparticles in the exposure chamber twice daily for 2 hours for 5 days. The mean particulate matter (PM) 10 concentration in the exposure chamber was 331 ± 83 μg/m3. The score of corneal fluorescein staining for evaluating ocular surface damage and the size of cervical lymph nodes for evaluating the immune response in the lymphatic drainage pathway were measured. The expression of the nucleotide-binding domain leucine-rich repeats, pyrin domain-containing 3 (NLRP3) inflammasome complex (NLRP3, apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (CARD) domain [ASC], and caspase-1) and IL-1β was quantitatively evaluated. Results: In the TiO2-exposed group, the mean corneal stain score was significantly increased compared to that of the control group (p = 0.002), and the size of the cervical lymph nodes in the TiO2-exposed group was greater than that of the control group (p = 0.004). The expression of NLRP3 and ASC was significantly increased in the corneo-conjunctival tissue and cervical lymph nodes after TiO2 exposure (both, p = 0.037). Inactive precursor forms of caspase-1 and IL-1β were decreased, but active forms of caspase-1 and IL-1β were increased after TiO2 exposure (both, p = 0.037). Conclusions: When the ocular surface was exposed to ambient particulate matter, the signal pathway of the NLRP3 inflammasome complex was activated, resulting in increased expression of the proinflammatory cytokine, IL-1β. The results suggested that the NLRP3 inflammasome complex was involved in the pathogenesis of ocular surface inflammation caused by exposure to particulate matter. KCI Citation Count: 1