Poly I:C Exacerbates Airway Inflammation and Remodeling in Cigarette Smoke-Exposed Mice

Abstract

Background Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disorder characterized by chronic inflammation and airway remodeling. Cigarette smoke (CS) and respiratory viruses are major causes of COPD development and exacerbation, but the mechanisms of these compounding factors on inflammation and pathological changes in airway structure still need further investigation. Purpose This work aimed to investigate the effects and mechanisms of Poly I:C on pathological changes in CS-induced COPD mice, such as airway inflammation and remodeling. Methods From 1 to 8 weeks, the mice were exposed to CS, Poly I:C, or a combination of both. To compare the pathological changes among different groups over time, the mice were sacrificed at week 4, 8, 16, and 24, then the lungs were harvested to measure pulmonary pathology, inflammatory cytokines, and airway remodeling. Results Our data revealed that the fundamental characteristics of COPD, such as pulmonary pathological damage, the release of inflammatory mediators, and the remodeling of airway walls, were observed at week 8 in CS-exposed mice and these pathological changes persisted to week 16. Compared with the CS group, the pathological changes, including decreased lung function, inflammatory cell infiltration, alveolar destruction, and airway wall thickening, were weaker in the Poly I:C group. These pathological changes were observed at week 8 and persisted to week 16 in Poly I:C-induced mice. Furthermore, Poly I:C exacerbated lung tissue damage in CS-induced COPD mice. The decreased lung function, airway inflammation and remodeling were observed in the combined group at week 4, and these pathological changes persisted to week 24. Our research indicated that Poly I:C enhanced the expression of p-P38, p-JNK and p-NF-κB in CS-exposed mice. Conclusion Poly I:C could promote airway inflammation and remodeling in CS-induced COPD mice probably by NF-κB and MAPK signaling.

Association among Lifestyle and Risk Factors with SARS-CoV-2 Infection

“…Smoking also causes oxidative stress and inflammatory activities in the lung, affecting airway permeability (leaky lung) and angiotensin-converting enzyme 2 (ACE2) expression. 8 The ACE2 receptor is the site of SARS-CoV2 virus entry into the host cell, since the S2 domain of the viral spiked envelope has a high affinity for the receptor. It is shown that smoking up regulates ACE-2 receptor in the lung epithelium.…”

Adding (Viral) Insult to (Smoke) Injury may Prolong COPD Changes After Smoking Cessation

“…In conclusion, viral infections may potentiate cigarette smoke-induced injury and significantly prolong inflammation and airway remodeling, even after smoking cessation. The paper by Li et al ( 8 ) supports that viral infections in COPD patients can cause more than just a temporary setback. Perhaps it is time to focus more on the COPD lung virome and find ways to monitor and treat viral infections in these patients, in order to give their lungs a chance to heal.…”

“…Much less is known about the potential chronic impact of recurrent viral infections in COPD development and persistence. This gap is addressed by the work of Li et al, in this issue of LUNG [ 8 ]. The authors utilize a cigarette smoke/immune activation (through poly-I:C administration) model, to demonstrate that combination exposure exacerbates inflammatory and remodeling changes beyond what either exposure alone achieves.…”

“…The authors utilize a cigarette smoke/immune activation (through poly-I:C administration) model, to demonstrate that combination exposure exacerbates inflammatory and remodeling changes beyond what either exposure alone achieves. Furthermore, they demonstrate these effects to be more persistent in the case of co-exposure: in this model, inflammatory and remodeling changes persisted for several weeks even after smoke exposure and poly-I:C administration were stopped [ 8 ]. This is a significant finding which may have major implications in the prognosis of COPD patients even after smoking cessation.…”

LUNG Year in Review: 2022

“…Studies of obstructive airway disease comprised a significant portion of articles published is 2022. Clinical studies of COPD examined diagnosis [ 2 ], risk factors [ 3 ], predictors of outcomes [ 4 – 9 ], and therapeutic interventions [ 10 , 11 ], whereas preclinical investigations evaluated chronic cigarette smoke-induced inflammation and airway remodeling [ 12 , 13 ]. Contributions in the field of asthma included physiological studies [ 14 – 18 ], effects of therapeutic interventions [ 19 ], social determinants of clinical outcomes [ 20 ], asthma-associated cough [ 21 , 22 ] and preclinical investigations [ 23 ].…”