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HMGB1 in the pathogenesis of ultraviolet-induced ocular surface inflammation

 SJ Han  ;  HJ Min  ;  SC Yoon  ;  EA Ko  ;  SJ Park  ;  J-H Yoon  ;  J-S Shin  ;  KY Seo 
 CELL DEATH & DISEASE, Vol.6 : 1863, 2015 
Journal Title
Issue Date
Animals ; Cell Line ; Cell Nucleus/metabolism ; Cell Nucleus/radiation effects ; Conjunctiva/metabolism ; Conjunctiva/pathology ; Conjunctiva/radiation effects* ; Cytoplasm/metabolism ; Cytoplasm/radiation effects ; Epithelial Cells/metabolism ; Epithelial Cells/pathology ; Epithelial Cells/radiation effects* ; Female ; Gene Expression ; HMGB1 Protein/genetics ; HMGB1 Protein/metabolism* ; Humans ; Inflammation ; Mice ; Mice, Inbred BALB C ; Protein Transport ; Pterygium/etiology ; Pterygium/genetics ; Pterygium/metabolism* ; Pterygium/pathology ; Reactive Oxygen Species/agonists ; Reactive Oxygen Species/metabolism* ; Receptor for Advanced Glycation End Products/chemistry ; Receptor for Advanced Glycation End Products/genetics ; Receptor for Advanced Glycation End Products/metabolism ; Signal Transduction ; Ultraviolet Rays/adverse effects*
High-mobility group box 1 (HMGB1) functions as a transcription-enhancing nuclear protein as well as a crucial cytokine that regulates inflammation. This study demonstrated that secretion of HMGB1 due to ultraviolet (UV) radiation inducing ocular surface inflammation-mediated reactive oxygen species (ROS) production. After treating conjunctival epithelial cells with UV radiation, HMGB1 was translocated from the nucleus to the cytoplasm and then eventually to the extracellular space. HMGB1 played a crucial role in UV-induced conjunctival neutrophil infiltration, which subsided when mice were pretreated with the HMGB1 inhibitors soluble receptor for advanced glycation endproducts (sRAGEs) and HMGB1 A box protein. In case of using ROS quencher, there was decrease in UV-induced HMGB1 secretion in conjunctival epithelial cells and mice. Considering that UV-induced chronic inflammation causes ocular surface change as pterygium, we have confirmed high HMGB1 translocation and ROS expression in human pterygium. Our findings therefore revealed a previously unknown mechanism of UV-induced ocular inflammation related to ROS and HMGB1 suggesting a new medical therapeutic target.
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1. College of Medicine (의과대학) > Dept. of Medical Humanities and Social Sciences (인문사회의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Seo, Kyoung Yul(서경률) ORCID logo https://orcid.org/0000-0002-9855-1980
Shin, Jeon Soo(신전수) ORCID logo https://orcid.org/0000-0002-8294-3234
Yoon, Sang Chul(윤상철) ORCID logo https://orcid.org/0000-0003-0454-9597
Yoon, Joo Heon(윤주헌)
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