中华行为医学与脑科学杂志
中華行為醫學與腦科學雜誌
중화행위의학여뇌과학잡지
CHINESE JOURNAL OF BEHAVIORAL MEDICINE AND BRAIN SCIENCE
2012年
10期
880-883
,共4页
张洪涛%修春明%牛洪泉%王云波%汤国太
張洪濤%脩春明%牛洪泉%王雲波%湯國太
장홍도%수춘명%우홍천%왕운파%탕국태
塞来昔布%胶质瘤%环氧化酶-2%微环境%树突状细胞
塞來昔佈%膠質瘤%環氧化酶-2%微環境%樹突狀細胞
새래석포%효질류%배양화매-2%미배경%수돌상세포
Celecoxib%Gliomas%Cyclooxygenase-2%Microenvironment%Dendritic cells
目的 探讨脑胶质瘤微环境及环氧化酶2抑制剂塞来昔布对树突状细胞( dendritic cell,DC)表型和功能的影响.方法 检测塞来昔布对C6细胞COX-2蛋白表达及PGE2分泌水平的影响.分离人外周血单个核细胞,分为正常诱导组、C6细胞上清组及塞来昔布+C6细胞上清组,体外诱导培养为DC细胞.观察DC形态学变化,检测DC表面分子CD80、CD83、CD86、CD1a的表达.检测DC培养上清中IL-12的水平及其体外刺激同种异体T细胞增殖能力.结果 塞来昔布可呈浓度依赖性下调C6细胞COX-2蛋白表达水平及PGE2分泌水平.各组细胞均可诱导出典型DC形态.三组DC CD1a表达率(％)为(75.56±2.40,75.09±3.67,76.03±3.43),CD83表达率(％)为(72.04 ±3.45,71.44±3.78,73.63 ±3.31),差异无统计学意义(P＞0.05),C6上清组DC CD80、CD86表达率(％)分别为(58.41 ±3.85,58.22±3.25),低于正常诱导组(分别为70.36±2.91,69.31±4.29),差异具有统计学意义(P＜0.01),对应其刺激T淋巴细胞增殖能力降低(P＜0.01),IL-12分泌水平(pg/ml)低于正常诱导组(分别为137.88±5.33,186.04±4.76),差异具有统计学意义(P＜0.01).塞来昔布预处理C6细胞后可提高CD80、CD86表达水平(66.83±2.51,63.51±5.47,P＜0.01)及刺激T淋巴细胞增殖能力、IL-12分泌水平(170.31±3.46,P＜0.01),但仍低于正常诱导组(P＜0.01).结论 塞来昔布可通过抑制COX-2蛋白活性,降低肿瘤局部微环境中的PGE2水平,改善DC的表型和功能.
目的 探討腦膠質瘤微環境及環氧化酶2抑製劑塞來昔佈對樹突狀細胞( dendritic cell,DC)錶型和功能的影響.方法 檢測塞來昔佈對C6細胞COX-2蛋白錶達及PGE2分泌水平的影響.分離人外週血單箇覈細胞,分為正常誘導組、C6細胞上清組及塞來昔佈+C6細胞上清組,體外誘導培養為DC細胞.觀察DC形態學變化,檢測DC錶麵分子CD80、CD83、CD86、CD1a的錶達.檢測DC培養上清中IL-12的水平及其體外刺激同種異體T細胞增殖能力.結果 塞來昔佈可呈濃度依賴性下調C6細胞COX-2蛋白錶達水平及PGE2分泌水平.各組細胞均可誘導齣典型DC形態.三組DC CD1a錶達率(％)為(75.56±2.40,75.09±3.67,76.03±3.43),CD83錶達率(％)為(72.04 ±3.45,71.44±3.78,73.63 ±3.31),差異無統計學意義(P＞0.05),C6上清組DC CD80、CD86錶達率(％)分彆為(58.41 ±3.85,58.22±3.25),低于正常誘導組(分彆為70.36±2.91,69.31±4.29),差異具有統計學意義(P＜0.01),對應其刺激T淋巴細胞增殖能力降低(P＜0.01),IL-12分泌水平(pg/ml)低于正常誘導組(分彆為137.88±5.33,186.04±4.76),差異具有統計學意義(P＜0.01).塞來昔佈預處理C6細胞後可提高CD80、CD86錶達水平(66.83±2.51,63.51±5.47,P＜0.01)及刺激T淋巴細胞增殖能力、IL-12分泌水平(170.31±3.46,P＜0.01),但仍低于正常誘導組(P＜0.01).結論 塞來昔佈可通過抑製COX-2蛋白活性,降低腫瘤跼部微環境中的PGE2水平,改善DC的錶型和功能.
목적 탐토뇌효질류미배경급배양화매2억제제새래석포대수돌상세포( dendritic cell,DC)표형화공능적영향.방법 검측새래석포대C6세포COX-2단백표체급PGE2분비수평적영향.분리인외주혈단개핵세포,분위정상유도조、C6세포상청조급새래석포+C6세포상청조,체외유도배양위DC세포.관찰DC형태학변화,검측DC표면분자CD80、CD83、CD86、CD1a적표체.검측DC배양상청중IL-12적수평급기체외자격동충이체T세포증식능력.결과 새래석포가정농도의뢰성하조C6세포COX-2단백표체수평급PGE2분비수평.각조세포균가유도출전형DC형태.삼조DC CD1a표체솔(％)위(75.56±2.40,75.09±3.67,76.03±3.43),CD83표체솔(％)위(72.04 ±3.45,71.44±3.78,73.63 ±3.31),차이무통계학의의(P＞0.05),C6상청조DC CD80、CD86표체솔(％)분별위(58.41 ±3.85,58.22±3.25),저우정상유도조(분별위70.36±2.91,69.31±4.29),차이구유통계학의의(P＜0.01),대응기자격T림파세포증식능력강저(P＜0.01),IL-12분비수평(pg/ml)저우정상유도조(분별위137.88±5.33,186.04±4.76),차이구유통계학의의(P＜0.01).새래석포예처리C6세포후가제고CD80、CD86표체수평(66.83±2.51,63.51±5.47,P＜0.01)급자격T림파세포증식능력、IL-12분비수평(170.31±3.46,P＜0.01),단잉저우정상유도조(P＜0.01).결론 새래석포가통과억제COX-2단백활성,강저종류국부미배경중적PGE2수평,개선DC적표형화공능.
Objective To investigate the effects of glioma microenvironment and COX-2 inhibitor celecoxib on the phenotypes and function of dendritic cell (DC).Methods The expression of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) production were detected in glioma C6 cells treated with different concentration of celecoxib.Monocytes were isolated from human peripheral blood and cultured with 200 ng/ml rhGM-CSF and 50 ng/ml rhIL-4,either C6 tumor cells supernatant (TSN) or TSN from C6 cells treated with celecoxib to generate DCs.Cell morphology was observed.Cell phenotype including CD1a,CD80,CD83 and D86 were analyzed on a FACScan.Production of IL-12 in DC supernatant and the potential to stmiulate allogeneic T cell proliferation were detected.Results The expression of COX-2 and PGE2 production in C6 cells decreased after treated with celecoxib in a concentration dependant manner.Typical DCs were induced in all groups and the expression of CD1a ((75.56±2.40)％,(75.09±3.67)％,(76.03 ±3.43)％),CD83((72.04±3.45)％,(71.44±3.78)％,( 73.63 ± 3.31 ) ％ ) had no difference (P ＞ 0.05 ).Expression of CD80 ( ( 58.41 ± 3.85 ) ％ ),CD86 ( ( 58.22 ±3.25)％ ) in DC with TSN obviously decreased compared with normal group( (70.36 ± 2.91 )％,(69.31 ±4.29 ) ％,P ＜ 0.01 ) as well as the IL-12 production ( ( 137.88 ± 5.33 ) pg/ml,( 186.04 ± 4.76 ) pg/ml) and the potential to stmiulate allogeneic T cell proliferation ( P ＜ 0.01 ).Celecoxib increased the expression of CD80,CD86 (66.83 ± 2.51,63.51 ± 5.47,P＜ 0.01 ) in DC and the same as IL-12 production( ( 170.31 ± 3.46) pg/ml,P ＜ 0.01 ) and the potential to stmiulate allogeneic T cell proliferation ( P ＜ 0.01 ),which were lower than the normal level.Conclusion Glioma microenvironment may induce the celecoxib can inhibit the expression of COX-2 and PGE2 in gliomas cells and improve the phenotypes and function defect of DCs.
