ADAM17 and EGFR regulate IL-6 receptor and amphiregulin mRNA expression and release in cigarette smoke-exposed primary bronchial epithelial cells from patients with chronic obstructive pulmonary disease (COPD)

• DOI: 10.14814/phy2.12878
• Publication Date: 2016-08-26T00:07:36Z
• Authors: Marta Stolarczyk; Gimano D. Amatngalim; Xiao Yu; Mieke Veltman; Pieter S. Hiemstra; Bob J. Scholte
• Keywords: Male; Nicotiana; 0301 basic medicine; Bronchi; ADAM17 Protein; Amphiregulin; Pulmonary Disease, Chronic Obstructive; 03 medical and health sciences; Humans; RNA, Messenger; amphiregulin (AREG); Original Research; Aged; TACE; Inhalation Exposure; Smoking; EMC MGC-02-13-02; Epithelial Cells; Middle Aged; Tyrphostins; epidermal growth factor receptor (EGFR); Receptors, Interleukin-6; 3. Good health; ErbB Receptors; A disintegrin and metalloprotease 17 (ADAM17); IL6 receptor (IL6R); Quinazolines; Airway Remodeling; Female; Chronic Obstructive Pulmonary Disease (COPD); Signal Transduction

Aberrant activity of a disintegrin and metalloprotease 17 (ADAM17), also known as TACE, epidermal growth factor receptor (EGFR) has been suggested to contribute chronic obstructive pulmonary disease (COPD) development progression. The aim this study was investigate the role these proteins in activation primary bronchial epithelial cells differentiated at air-liquid interface (ALI-PBEC) by whole cigarette smoke (CS), comparing from COPD patients with non-COPD CS exposure ALI-PBEC enhanced ADAM17-mediated shedding IL-6 (IL6R) EGFR agonist amphiregulin (AREG) toward basolateral compartment, which more pronounced than controls. transiently increased IL6R AREG mRNA similar extent cultures both groups, suggesting that posttranslational events determine differential between cultures. We show for first time situ proximity ligation (PLA) strongly enhances interactions phosphorylated ADAM17 IL-6R an intracellular CS-induced trafficking precede extracellular compartment. Both protein expression, demonstrated using selective inhibitors (AG1478 TMI-2). Our data are consistent autocrine-positive feedback mechanism triggers agonists evoking activation, ADAM17-dependent manner, subsequently transduce paracrine signaling myeloid connective tissue. Reducing could therefore be therapeutic approach tissue remodeling inflammation observed COPD.