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  • Title: [Erythromycin restores oxidative stress-induced corticosteroid responsiveness of human THP-1 cells by up-regulating the expression of histone deacetylase 2].
    Author: Zhang Y, He Z, Sun X, Li Z, Zhao L, Mao C, Huang D, Zhang J, Zhong X.
    Journal: Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi; 2014 Apr; 30(4):384-7. PubMed ID: 24721407.
    Abstract:
    OBJECTIVE: To investigate the effect of erythromycin (EM) on corticosteroid insensitivity of human THP-1 cells induced by cigarette smoke extract (CSE) and its mechanism. METHODS: THP-1 cells were treated with EM followed by CSE stimulation. Histone deacetylase-2 (HDAC2) short interference RNA (HDAC2-siRNA) was transfected into the cells using Lipofectamine(TM); 2000. Interleukin-8 (IL-8) level in supernatants was measured by ELISA and HDAC2 expression was determined by real-time quantitative PCR (qRT-PCR) and Western blotting. RESULTS: The inhibition ratio of IL-8 in the EM group was significantly higher than that in the CSE group, but lower than that in the control group (P<0.05). The half-maximal inhibitory concentration of dexamethasone (IC50;-Dex) in the EM group was lower than that in the CSE group, but higher than that in the control group (P<0.05). The expression of HDAC2 protein in the EM group was higher than that in the CSE group, but lower than that in the control group (P<0.05). Besides, HDAC2 mRNA and HDAC2 protein expressions were lower in the HDAC2-siRNA group than in the scrambled oligonucleotide (SC) group. EM could reverse HDAC2 mRNA and HDAC2 protein reduction induced by HDAC2-siRNA (P<0.05). CONCLUSION: Corticosteroid sensitivity of THP-1 cells could be reduced by CSE. EM could reverse the corticosteroid insensitivity by up-regulating the expression of HDAC2 protein.
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