Klotho Reduction in Alveolar Macrophages Contributes to Cigarette Smoke Extract-induced Inflammation in Chronic Obstructive Pulmonary Disease

Abstract

Background:The role of Klotho in airway inflammation in COPD remains unclear. Results: Klotho expression was reduced in alveolar macrophages in peripheral lungs and PBMCs of smokers with and without COPD. Klotho regulates macrophage inflammation via NF-B pathway. Conclusion: Klotho plays a role in sustained inflammation of the lungs. Significance: These findings suggest Klotho may have therapeutic implications in COPD.

Lung ageing and COPD: is there a role for ageing in abnormal tissue repair?

“…Aged animals had increased lung inflammation, with higher levels of inflammatory cells and mediators associated with lower repair. Two studies from 2015 observed that Klotho, an anti-ageing protein with anti-inflammatory properties, is reduced in alveolar macrophages [111] and airway epithelial cells of patients with COPD [112]. The reduction was associated with high levels of oxidative stress, inflammation and apoptosis [111,112].…”

Klotho and smoking – An interplay influencing the skeletal muscle function deficits that occur in COPD

“…More recently, it has been demonstrated that Klotho is reduced in the airway epithelial cells and alveolar macrophages of both smokers and COPD patients (12,13) and that cigarette smoke reduces Klotho expression which subsequently confers augmented inflammation (13). Putative roles for smoking and physical activity in the aetiology of skeletal muscle weakness are not mutually exclusive.…”

“…Li et al demonstrated that knockdown of endogenous Klotho augments the expression of inflammatory mediators, including MMP-9, IL-6 and TNF-alpha by alveolar macrophages and that exogenous Klotho inhibited the expression of cigarette smoke induced inflammation (13). This group extended their work to demonstrate Klotho depletion increases sensitivity to cigarette smoke-induced inflammation and oxidative stress-induced cell damage in epithelial cells where these effects involved the nuclear factor κB, mitogen-activated protein kinase and nuclear factor erythroid 2-related factor 2 pathways (12).…”

“…Furthermore, current smoking status seems to attenuate circulating (14,15) and airway (12,13) Klotho levels. Since in developed countries smoking is the usual aetiological factor in COPD, a pathophysiological role for Klotho signalling in the development of skeletal muscle function deficits is possible; however there are currently no data available on human Klotho protein within skeletal muscle.…”

“…Very recently, systemic Klotho levels and airway Klotho expression have been demonstrated to be lower in patients with COPD but the relevance to skeletal muscle function was not assessed (12,13).…”