title: Erythromycin enhances the anti-inflammatory activity of budesonide in COPD rat model.
abstract: Glucocorticoids (GCs) have been widely applied to treat patients with chronic obstructive pulmonary disease (COPD). But the effect of GCs was not ideal. This study was to observe whether erythromycin could enhance the anti-inflammatory activity of budesonide in COPD model rats and to explore the mechanism involved. In this study, male Sprague-Dawley rats were divided into five groups: healthy control group (H group), COPD model group (C group), erythromycin group (E group), budesonide group (B group) and erythromycin + budesonide group (E+B group). The rats in groups of C, E, B and E+B were developed into COPD models. Different groups were given different drug interventions. The levels of 8-iso-PGF2α, IL-8, and TNF-α in BALF and serum were measured with ELISA. The protein expression levels of HDAC2, PI3K, and p-AKT in lung tissue were measured with Western-blot and immunohistochemistry. The levels of 8-iso-PGF2α, IL-8, and TNF-α in BALF and serum were lower in E+B group than those in B group and C group (all P<0.001).The protein expression level of HDAC2 was higher and PI3K and p-AKT were lower in E+B group than those in B group and C group (all P<0.001). Moreover, the expression levels of HDAC2 were negatively correlated with the levels of 8-iso-PGF2α, IL-8 and TNF-α both in serum and BALF and the expression levels of PI3K and p-AKT among the five groups, with all P<0.001. We conclude that erythromycin can enhance the anti-inflammatory activity of budesonide in COPD model rats, possibly through inhibiting the PI3K/AKT pathway and enhancing the activity of HDAC2.
authors.affiliation: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450000, Henan Province, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Miao
authors.affiliation: Department of Respiratory Medicine, The Affiliated Hospital of Weifang Medical University Weifang 261031, Shandong Province, China.
authors.forename: Zengyan
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450000, Henan Province, China.
authors.forename: Fengxiang
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450000, Henan Province, China.
authors.forename: Shifu
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450000, Henan Province, China.
authors.forename: Ruixia
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450000, Henan Province, China.
authors.forename: Dongbo
authors.initials: D
authors.lastname: Ma
authors.affiliation: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450000, Henan Province, China.
authors.forename: Qiuge
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450000, Henan Province, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450000, Henan Province, China.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450000, Henan Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
keywords: Budesonide; PI3K/AKT; chronic obstructive pulmonary disease; erythromycin; histone deacetylase 2