Inhibition of erythromycin on TNF-α release from human macrophages stimulated by cigarette smoke
QIU Jufeng
LI Meihua
ZHONG Xiaoning
WEN Mingzhi
MA Nan
TANG Xiaojuan
HUANG Mei
LIANG Quan
Abstract：Objective To investigate the inhibitory effect of erythromycin on the TNF-α release of human macrophages stimulated by cigarette smoke and its possible mechanism. Methods The human monocytic cell line U937 cells were differentiated into human macrophages by Phorbol esters (PMA). The cigarette smoke extract (CSE) (0. 1, 1, 2. 5％) and erythromycin (EM) (0. 1, 1, 10 μg/mL) were used to deal with the macrophages at different time points (24, 48, and 72 h) , respectively, and we chose the time and concentrations with the least effect on proliferation activity of macrophages. The 1 μg/mL CSE, 1％ EM and 24-hour treatment time were selected for the experiment. The differentiated U937 cells were randomly divided into four groups: the control group (with no intervention) , CSE group (1％ CSE stimulation for 24 h) , CSE + EM group (pre-incubation with 1 μg/ml EM for 24 h before 1％ CSE stimulation for 24 h) , and TSA group(TSA stimulation for 24 h). The TNF-α level in the culture supernatants was measured by ELISA; Western blotting was used to measure the expression of the histone deacetylase-1(HDAC1) and NF-κB protein. Results The level of TNF-α in the culture supernatants of the control group, CSE group, and CSE + EM group were (274. 96 ± 182. 39) , (744. 46 ± 638. 38) , and (646. 57 ± 603. 53) pg/mL, respectively (all P＜0. 05). Compared with the control group, the expression of HDAC1 protein in the CSE group, EM + CSE group, and TSA group decreased, and the expression of NF-κB protein increased(all P＜0. 05). Compared with the CSE group, the expression of HDAC1 protein increased, and the expression of NF-κB protein decreased in the EM + CSE group (both P < 0. 05). Compared with the EM + CSE group, the expression of HDAC1 protein in the TSA group decreased, and the expression of NF-κB protein increased (both P < 0. 05). Conclusions EM inhibits the release of TNF-α of human macrophages induced by cigarette smoke. The mechanism is that EM may restore the expression of HDAC1 and inhibit the expression of NF-κB, which decreases the release of TNF-α and thus alleviates the inflammatory response.
Keywords：chronic obstructive pulmonary diseaseerythromycincigarette smokeexposureinflammatory responsetumor necrosis factor-αhistone deacetylase 1
Publication Date：2018-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：4( 22-25 )