Instituto de Investigación Sanitaria de Les Illes Balears (IdISBa), Hospital Universitario Son Espases, 07120 Palma de Mallorca, Spain.
Chest Diseases Department, Faculty of Medicine, Alexandria University, Alexandria 21526, Egypt.
Int J Mol Sci. 2022 Jul 23;23(15):8127. doi: 10.3390/ijms23158127.
Inhaled corticosteroids (ICS) use is associated with an increased risk of (PA) infection in patients with COPD. We aimed to evaluate the effects of ICS on alveolar macrophages in response to PA in COPD patients with and without baseline ICS treatment (COPD and COPD + ICS, respectively) as well as smoker and nonsmoker controls. To do so, cells were infected with PA and cotreated with budesonide (BUD) or fluticasone propionate (FLU). The analysis of NF-κB and c-jun activity revealed a significant increase in both factors in response to PA cotreated with BUD/FLU in smokers but not in COPD or COPD + ICS patients when compared with PA infection alone. The expression of Toll-like receptor 2 (TLR2) and the transcription factor c-jun were induced upon PA infection in nonsmokers only. Moreover, in the smoker and COPD groups, there was a significant increase in TLR2 and a decrease in c-jun expression when treated with BUD/FLU after PA infection, which were not observed in COPD + ICS patients. Therefore, the chronic use of ICS seemingly makes the macrophages tolerant to BUD/FLU stimulation compared with those from patients not treated with ICS, promoting an impaired recognition of PA and activity of alveolar macrophages in terms of altered expression of TLR2 and cytokine production, which could explain the increased risk of PA infection in COPD patients under ICS treatment.
吸入性皮质类固醇（ICS）的使用与 COPD 患者中肺炎克雷伯菌（PA）感染的风险增加有关。我们旨在评估 ICS 对 COPD 患者（ICS 治疗前和 ICS 治疗后分别为 COPD 和 COPD+ICS）以及吸烟者和非吸烟者对照肺泡巨噬细胞对 PA 的反应的影响。为此，用 PA 感染细胞，并与布地奈德（BUD）或丙酸氟替卡松（FLU）共同处理。NF-κB 和 c-jun 活性分析显示，与单独 PA 感染相比，在吸烟者中，与 BUD/FLU 共同处理后，两种因子均显著增加，但在 COPD 或 COPD+ICS 患者中则没有增加。只有在非吸烟者中，PA 感染会诱导 Toll 样受体 2（TLR2）和转录因子 c-jun 的表达。此外，在吸烟者和 COPD 组中，在 PA 感染后用 BUD/FLU 处理时，TLR2 显著增加，而 c-jun 表达降低，但在 COPD+ICS 患者中则没有观察到这种情况。因此，与未接受 ICS 治疗的患者相比，ICS 的长期使用似乎使巨噬细胞对 BUD/FLU 刺激产生耐受，从而损害对 PA 的识别，并改变 TLR2 和细胞因子产生的表达，从而导致接受 ICS 治疗的 COPD 患者 PA 感染风险增加。
