Aerobic exercise alleviates ventilator-induced lung injury by inhibiting NLRP3 inflammasome activation

Abstract

Background Ventilator-induced lung injury (VILI) is caused by stretch stimulation and other factors related to mechanical ventilation (MV). NOD-like receptor protein 3 (NLRP3), an important innate immune component, is strongly associated with VILI. This study aimed to investigate the effect and mechanisms of aerobic exercise (EX) on VILI. Methods To test the effects of the PKC inhibitor bisindolylmaleimide I on PKC and NLRP3, male C57BL/6 mice (7 weeks old, 19 ~ 23 g) were randomly divided into four groups: control group(C), bisindolylmaleimide I-pretreated group(B), MV group, and bisindolylmaleimide I-pretreated + MV (B + MV) group. The mice were pretreated with bisindolylmaleimide I through intraperitoneal injection (0.02 mg/kg) 1 h before MV. MV was performed at a high tidal volume (30 ml/kg). To explore the ameliorative effect of EX on VILI, the mice were randomly divided into C group, MV group, EX group and EX + MV group and subjected to either MV or 5 weeks of EX training. After ventilation, haematoxylin-eosin (HE) staining and wet/dry weight ratio was used to assess lung pathophysiological changes. PKCɑ, P-PKCɑ, ASC, procaspase-1, caspase-1, pro-IL-1β, IL-1β, NLRP3 and occludin (tight junction protein) expression in lung tissues was determined by Western blotting. The level of IL-6 in alveolar lavage fluid was determined by ELISA. Results NLRP3, P-PKCɑ, and PKCɑ levels were inceased in MV group, but bisindolylmaleimide I treatment reversed these changes. Inhibition of PKC production prevented NLRP3 activation. Moreover, MV increased ASC, procaspase-1, caspase-1, pro-IL-1β, and IL1β levels and decreased occludin levels, but EX alleviated these changes. HE staining and lung injury scoring confirmed an absence of obvious lung injury in C group and EX group. Lung injury was most severe in MV group but was improved in EX + MV group. Overall, these findings suggest that MV activates the NLRP3 inflammasome by activating PKCɑ and inducing occludin degradation, while Exercise attenuates NLRP3 inflammasome and PKCɑ activation. Besides, exercise improves cyclic stretch-induced degradation of occludin. Conclusion PKC activation can increase the level of NLRP3, which can lead to lung injury. Exercise can reduce lung injury by inhibiting PKCɑ and NLRP3 activation. Exercise maybe a potential measure for clinical prevention of VILI.

Immunological studies on acupuncture and moxibustion treatment of rheumatoid arthritis: A review

“…[ 39 ] In the process of RA, a variety of intersecting pathophysiological systems such as autoimmune inflammation and endocrine disorders jointly form an intricate NEI network. [ 40 ] Yang F et al found that the foot swelling of AA rats was reduced after manual acupuncture of ST36, the levels of TNF-α protein and other pro-inflammatory factors in the ankle joint were down-regulated, and the cellular immune network in the inflammatory site was enhanced (the cell network density was 230.00 on the first day of acupuncture; Cellular network densities at days 7 and 15 were 40.82 and 86.76, respectively), demonstrating that acupuncture can increase the strength of immune effects on target organs, and at the same time promote the differentiation of macrophages in the joint site to the M2 phenotype, and secrete cytokines that inhibit inflammation and promote tissue repair. [ 41 ] Ding Shasha et al observed 32 common signaling molecules of NEI network in the serum of 131 Wistar rats.…”