CAJ | 학술논문

目的：探讨蛋白激酶G（PKG）对THP-1巨噬细胞源性泡沫细胞中炎症因子[白介素-6（IL-6）、白介素-10（IL-10）、肿瘤坏死因子-α（TNF-α）]分泌的影响。方法：THP-1单核细胞用160 nmol/L的佛波酯诱导分化成巨噬细胞，再以50 mg/L氧化低密度脂蛋白（ox-LDL）处理形成泡沫细胞，油红“O”染色，镜下观察细胞形态。以PKG激动剂100μmol/L 8-Br-cGMP和抑制剂2μmol/L KT-5823分别处理巨噬细胞和泡沫细胞，同时设立巨噬细胞正常对照组和泡沫细胞模型对照组，24 h后收集细胞上清液，ELISA检测各组细胞IL-6、IL-10、TNF-α的分泌。结果：ox-LDL处理巨噬细胞48 h后，成功构建为泡沫细胞。泡沫细胞中IL-6、TNF-α分泌显著增加（P＜0．05）。8-Br-cGMP处理巨噬细胞后，IL-6分泌显著减少（P＜0．05），IL-10分泌显著增加（P＜0．05）；KT-5823处理巨噬细胞后，IL-10分泌显著减少（P＜0．05）。8-Br-cGMP处理泡沫细胞后，IL-6和TNF-α分泌显著减少（P＜0．05），IL-10分泌显著增加（P＜0．05）；KT-5823处理泡沫细胞后，IL-6和TNF-α分泌显著减少（P＜0．05）。结论：PKG可能通过上调抗炎因子IL-10的表达、下调促炎因子IL-6和TNF-α的表达，抑制炎症的发生发展；PKG可作为潜在的抗动脉粥样硬化的新思路和新靶点。
목적：탐토단백격매G（PKG）대THP-1거서세포원성포말세포중염증인자[백개소-6（IL-6）、백개소-10（IL-10）、종류배사인자-α（TNF-α）]분비적영향。방법：THP-1단핵세포용160 nmol/L적불파지유도분화성거서세포，재이50 mg/L양화저밀도지단백（ox-LDL）처리형성포말세포，유홍“O”염색，경하관찰세포형태。이PKG격동제100μmol/L 8-Br-cGMP화억제제2μmol/L KT-5823분별처리거서세포화포말세포，동시설립거서세포정상대조조화포말세포모형대조조，24 h후수집세포상청액，ELISA검측각조세포IL-6、IL-10、TNF-α적분비。결과：ox-LDL처리거서세포48 h후，성공구건위포말세포。포말세포중IL-6、TNF-α분비현저증가（P＜0．05）。8-Br-cGMP처리거서세포후，IL-6분비현저감소（P＜0．05），IL-10분비현저증가（P＜0．05）；KT-5823처리거서세포후，IL-10분비현저감소（P＜0．05）。8-Br-cGMP처리포말세포후，IL-6화TNF-α분비현저감소（P＜0．05），IL-10분비현저증가（P＜0．05）；KT-5823처리포말세포후，IL-6화TNF-α분비현저감소（P＜0．05）。결론：PKG가능통과상조항염인자IL-10적표체、하조촉염인자IL-6화TNF-α적표체，억제염증적발생발전；PKG가작위잠재적항동맥죽양경화적신사로화신파점。
Objective To investigate the effect of PKG on the secretion of IL-6, IL-10, and TNF-αin THP-1 macrophage-derived foam cells. Methods THP-1 monocytes were induced to construct macrophages by treating with 160 nmol/L TPA. Then the macrophages were further treated with 50 mg/L ox-LDL to become foam cells. Four groups were set in this study, including the macrophage group, the foam cell group, the group of foam cell treated with PKG agonist 8-Br-cGMP, and the group of foam cell treated with PKG inhibitor KT-5823. The morphology of THP-1 cells, macrophages and foam cells were observed under microscope. The cellular lipid accumulation was detected by oil red ostaining. The secretion of IL-6, IL-10, and TNF-α into the supernatant was detected by ELISA assay. Results The foam cell was obtained after macrophage incubated with ox-LDL for 48 hours. The secretion of IL-6 and TNF-α increased significantly from the foam cells than that from the macrophages (P<0.05). After the THP-1 monocyte-derived macrophages were incubated with 8-Br-cGMP, the secretion of IL-6 in the supernatant decreased significantly ( P < 0 . 05 ) and IL-10 level in the supernatant increased significantly (P < 0.05). After the macrophages were incubated with KT-5823, the secretion of IL-10 decreased significantly (P<0.05), but the secretion of IL-6 was not significantly changed (P>0.05). After incubation with 8-Br-cGMP, the secretion of IL-6 and TNF-α from the macrophage-derived foam cells decreased significantly (P < 0.05), but IL-10 increased significantly (P<0.05). After the foam cells were treated with KT-5823, the secretion of IL-6 and TNF-αwere also decreased significantly (P<0.05), with no significant change of IL-10 secretion (P > 0.05). Conclusions PKG may enhance the expression of anti-inflammatory cytokine IL-10, and inhibit the expression of inflammatory cytokine IL-6 and TNF-α, contributing to prevent the development of inflammation. PKG might have a potential anti-atherosclerosis effect.