红霉素衍生物LY267108在抑制单核细胞增殖过程中对核因子-κB活化的影响

Effect of erythromycin derivatives on activation of nuclear factor-kappa B during its inhibition procedure on monocyte proliferation

目的通过观察红霉素衍生物LY267108对单核细胞增殖和核因子-κB(NF-κB)表达的影响,探讨红霉素衍生物抗炎作用的机制。方法以红霉素为对照,用四氮唑盐(MTT)还原法观察LY267108对单核细胞增殖的影响;用反转录-聚合酶链式反应(RT-PCR)和Western Blot方法观察LY267108对单核细胞NF-κB表达的影响。结果LY267108和红霉素均可抑制单核细胞的增殖,其IC50值分别为154.9、493.4μmol.L-1;RT-PCR和Western Blot测定结果显示LY267108可抑制单核细胞NF-κB mRNA和蛋白的表达,并与剂量之间呈现负相关。结论红霉素衍生物LY267108的抗炎活性可能与其抑制炎症细胞增殖和影响NF-κB活化有关。

Objective To observe the effects of erythromycin derivative LY267108 on the proliferation and the expression of nuclear factor-kappa B（NF-κB）of monocyte and study the anti-inflammatory mechanism of erythromycin derivatives. Methods The effects of LY267108 on the proliferation were evaluated by monotetrazolium test assay （MTT assay） ;monocytes were exposed to 100 μmol·L^-1 TNF-α with or without pretreatment with 3, 10, 30 or 100 mg· L^-1 of LY267108 1 h at 37 ℃. The expression of NF-κB was observed by reverse transcription-polymerase chain reaction（RT-PCR） and by Western Blot. Results The proliferation of monocyte was inhibited by LY267108 and erythromycin with IC50 of 154. 9 μmol·L^-1 and 493.4 μmol·L^-1 , respectively; LY267108 decreased the expressions of NF-κB mRNA and protein in a doserelated fashion. Conclusions The anti-inflammatory activity of erythromycin derivatives maybe due partly to the interaction with the proliferation and NF-κB signaling pathway in inflammatory cells.