Melatonin induced suppression of ER stress and mitochondrial dysfunction inhibited NLRP3 inflammasome activation in COPD mice

Correlations among Pulmonary DJ-1, VDR and Nrf-2 in patients with Chronic Obstructive Pulmonary Disease: A Case-control Study

“…To our knowledge, Nrf-2 is a key transcription factor that regulates the downstream antioxidant defense system and exerts a significant function in COPD [23]. The previous in vivo experiment found that cigarette smoking, the primary cause of COPD, evoked ROS excessive production and Nrf-2 downregulation in the human lung alveolar epithelium cell line [24]. Meanwhile, our results indicated HO-1 and NOX-4 were increased in lungs of COPD patients.…”

Potential Effects of Melatonin and Micronutrients on Mitochondrial Dysfunction during a Cytokine Storm Typical of Oxidative/Inflammatory Diseases

“…In this sense, chronic obstructive pulmonary disease (COPD) is characterized by a strong prooxidant state and mitochondrial dysfunction, which causes the activation of the NLRP3 inflammasome and the consequent cytokine storm usually observed in this lung pathology. Regarding this, melatonin, administered in both an in vivo and in vitro model of COPD, activated the intracellular antioxidant thioredoxin-1, to inhibit the inflammasome activation and to restore the general antioxidant and anti-inflammatory state by several signaling pathways [ 119 ]. As for the prevention and treatment of COPD, melatonin may also be useful in both early stages and in more severe stages of COVID-19 and other respiratory diseases characterized by hyper-inflammation [ 120 , 121 , 122 ].…”

Roles of Inflammasome in Cigarette Smoke-Related Diseases and Physiopathological Disorders: Mechanisms and Therapeutic Opportunities

“…In vitro, Mortaz et al (38) found that cigarette smoke could increase the expression of caspase-1 and IL-1b in human alveolar epithelial cells, suggesting the potential role of inflammasome signaling in the pathogenesis of COPD. Thereafter, more studies further demonstrated cigarette smoke was able to activate NLRP3 inflammasome in human bronchial and alveolar epithelial cells, and the inflammasome activation was able to further increase the release of inflammatory cytokines (including IL-1b and IL-18) (21,22,26,27). Particularly, Mahalanobish et al (21) reported that the activation of NLRP3 inflammasome in alveolar epithelial might result from cigarette smoke induced endoplasmic reticulum (ER) stress and mitochondrial dysfunctions.…”

“…Thereafter, more studies further demonstrated cigarette smoke was able to activate NLRP3 inflammasome in human bronchial and alveolar epithelial cells, and the inflammasome activation was able to further increase the release of inflammatory cytokines (including IL-1b and IL-18) (21,22,26,27). Particularly, Mahalanobish et al (21) reported that the activation of NLRP3 inflammasome in alveolar epithelial might result from cigarette smoke induced endoplasmic reticulum (ER) stress and mitochondrial dysfunctions. Wang et al (27) found that cigarette smoke-induced inflammasome activation was triggered by oxidative stress injury and Ca 2+ influx in human bronchial and alveolar epithelial cells.…”