title: Update on molecular mechanisms of corticosteroid resistance in chronic obstructive pulmonary disease.
abstract: Chronic obstructive pulmonary disease (COPD) is an inflammatory and irreversible pulmonary disorder that is characterized by inflammation and airway destruction. In recent years, COPD has become a global epidemic due to increased air pollution and exposure to cigarette smoke. Current therapeutics using bronchiodialator and anti-inflammatory corticosteroids are most widely used for all patients with persistent COPD, but these approaches are disappointing due to limited improvement in symptom control and survival rate. More importantly, a certain number of COPD patients are resistant to the corticosteroid treatment and their symptoms worsen. Therefore, more effective anti-inflammatory drugs and combinational treatment are required. Understanding of the underlying molecular and immunological mechanisms is critical to developing new therapeutics. Lung inflammation and the released pro-inflammatory cytokines affect glucocorticoid receptor (GR), histone deacetylase 2 (HDAC2) and surfactant protein D (SP-D) activities in many cell types. Macrophages, neutrophils, airway epithelial cells and lymphocytes are involved in the induction of corticosteroid resistance. This review updated the recent advances in molecular and immunological mechanisms of steroid resistance among patients and animal models with COPD. Meanwhile we discussed novel therapeutic approaches in controlling lung inflammation and improving corticosteroid sensitivity among the steroid resistant patients with COPD.
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China. Electronic address: jiangzl12@yahoo.com.
authors.forename: Zhilong
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China. Electronic address: zhu.lei@zs-hospital.sh.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001993:Bronchodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004351:Drug Resistance; D056464:Histone Deacetylase 2 / Q000378:metabolism; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism
chemical_list: D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D037663:Pulmonary Surfactant-Associated Protein D; D011965:Receptors, Glucocorticoid; C533423:HDAC2 protein, human; D056464:Histone Deacetylase 2
keywords: Chronic obstructive pulmonary disease (COPD); Corticosteroid resistance; Glucocorticoid receptor (GR); Histone deacetylase 2 (HDAC2); Surfactant protein D (SP-D)