期刊
SCIENTIFIC REPORTS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41598-022-20177-9
关键词
-
资金
- National Institutes of Health USA [R01 EY019470]
- American Society for Investigative Pathology Summer Research Opportunity Program in Pathology
- Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway
- Faculty of Medicine, University of Oslo, Norway
- Norwegian Research Council
There are differences in the responses of conjunctival goblet cells (CGCs) to inflammatory stimuli between males and females, and these responses are influenced by sex hormones. Males have a higher response to a specific pro-resolution lipid SPM, indicating that they may terminate inflammation in conjunctival goblet cells faster than females.
Many conjunctival inflammatory diseases differ between the sexes and altered conjunctival goblet cells (CGCs) response is often involved. Inflammation is initiated by the release of pro-inflammatory mediators and terminated by the biosynthesis of specialized pro-resolution mediators (SPMs). Herein, we determined the sex-based difference in the responses of CGCs to inflammatory stimuli or pro-resolving lipid SPMs and their interaction with sex hormones. GCs were cultured from pieces of human conjunctiva in RPMI media. CGCs were transferred 24 h before the start of experiments to phenol red-free and FBS-free media to minimize exogenous hormones. RT-PCR, immunofluorescence microscopy (IF), and Western Blot (WB) were performed to determine the presence of sex hormone receptors. Cellular response to pro-inflammatory stimuli or SPMs was studied by measuring the increase in intracellular [Ca2+] ([Ca2+](i)) using fura 2/AM microscopy. Use of RT-PCR demonstrated estrogen receptor (ER) alpha in 4/5 males and 3/3 females; ER beta in 2/4 males and 2/3 females; and androgen receptors (AR) in 3/3 male and 3/3 female CGCs. Positive immunoreactivity by IF and protein expression by WB was detected using antibodies for the ER alpha and ER beta in 3/3 males and 3/3 females, while AR were only present in males. Significantly different Ca2+ responses between sexes were found with carbachol only at 10(-3) M, but not with histamine or leukotriene (LT) B-4 at any concentration used. Incubation with dihydrotestosterone (DHT), estrone (E1), or estradiol (E2) at 10(-7) M for 30 min significantly inhibited the LTB4-stimulated [Ca2+](i) increase in male and female CGCs. Incubation with DHT, E1, and E2 overnight significantly inhibited the LTB4 response in females, while DHT and E2 significantly inhibited the LTB4 response in males. The SPM lipoxin A(4) (LXA(4)) (10(-9)-10(-8) M), but not the resolvins D1 or D2, induced an [Ca2+](i) increase that was significantly higher in males compared to females. We conclude that male and female CGCs showed differences in the expression of sex hormone receptors. Treatment with sex hormones altered pro-inflammatory mediator LTB4-induced response. Males compared to females have a higher response to the omega-6-fatty acid derived SPM LXA(4), indicating males may terminate inflammation in conjunctival goblet cells faster than females.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据