[Erythromycin restores oxidative stress-induced corticosteroid responsiveness of human THP-1 cells by up-regulating the expression of histone deacetylase 2].
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).


CONCLUSIONS
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.
Department of Respiratory Medicine, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
Yang
Y
Zhang
Department of Respiratory Medicine, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
Zhiyi
Z
He
Department of Respiratory Medicine, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
Xuejiao
X
Sun
Department of Respiratory Medicine, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
Zhanhua
Z
Li
Medical Intensive Care Unit, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
Lin
L
Zhao
Department of Respiratory Medicine, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
Congzheng
C
Mao
Department of Respiratory Medicine, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
Dongmei
D
Huang
Department of Respiratory Medicine, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
Jianquan
J
Zhang
Department of Respiratory Medicine, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
Xiaoning
X
Zhong
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004917:Erythromycin / Q000494:pharmacology*; D056464:Histone Deacetylase 2 / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects; D014026:Nicotiana / Q000737:chemistry; D015854:Up-Regulation / Q000187:drug effects*
D000305:Adrenal Cortex Hormones; D012333:RNA, Messenger; D012906:Smoke; D004917:Erythromycin; D003907:Dexamethasone; D056464:Histone Deacetylase 2