Cigarette Smoke Suppresses Type I Interferon-Mediated Antiviral Immunity in Lung Fibroblast and Epithelial Cells

The objective of this study was to investigate the impact of cigarette smoke on innate antiviral defense mechanisms; specifically, we examined the effects of cigarette smoke on the induction of type I interferon (IFN). We observed a dose-dependent decrease in the ability of human lung fibroblast and epithelial cells to elicit an antiviral response against a viral double-strand RNA (dsRNA) mimic, polyI:C, in the presence of cigarette smoke-conditioned medium (SCM). Mechanistically, SCM decreases the expression of IFN-stimulated gene 15 (ISG15) and IFN regulatory factor-7 (IRF-7) transcripts and suppresses the nuclear translocation of key transcription factors, nuclear factor-κB (NF-κB) and IRF-3, after polyI:C stimulation. Furthermore, we provide evidence that the intercellular defense strategy against viral infection is also impaired. We observed a decrease in the ability of fibroblasts to elicit an antiviral state in response to IFN-β stimulation. This was associated with decreased nuclear translocation of phosphorylated Stat1 in response to IFN-β treatment. The effects elicited by SCM are reversible and are almost entirely abrogated in the presence of an antioxidant, such as glutathione. Our findings suggest that cigarette smoke affects the immediate-early, inductive, and amplification phases of the type I IFN response

Τι είναι η πατρίδα μας; [What is our fatherland?]

Ποια είναι η πατρίδα κάποιων; Ας δούμε το θέμα λίγο σαν πρόβλημα της φιλοσοφίας της γλώσσας: για ένα κατηγόρημα «Άγγλος» «Γάλλος», «Πορτογάλος», «Βέλγος», «Φλαμανδός», πώς να αποφασίσουμε ποια αντικείμενα (ποιοι άνθρωποι) εμπίπτουν σε ποιο κατηγόρημα; Έχουν τελικά νόημα αυτά τα κατηγορήματα; Η χρήση και κατάχρηση αυτών των κατηγορημάτων έχει αποτελέσει μια από τις κυριότερες πηγές δυστυχίας στη διάρκεια των δύο τελευταίων αιώνων και συνεχίζει να είναι στην ημερήσια διάταξη. Συνήθως εμφανίζεται στα πλαίσια αγώνων για την απόκτηση «ελευθερίας» σε αντιπαράθεση με την «καταπίεση», και σε παγκόσμιο επίπεδο και κοντύτερα μας: στη Μακεδονία, την Καταλονία, την Ιρλανδία, το Κουρδιστάν ... Νομίζω πώς αρκετά από αυτά βασίζονται σε λάθη

Role of BAFF in pulmonary autoantibody responses induced by chronic cigarette smoke exposure in mice

Emerging evidence suggests that autoimmune processes are implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). In this study, we assessed the expression of B-cell activating factor (BAFF) in smokers, and investigated the functional importance of BAFF in the induction and maintenance of cigarette smoke-induced pulmonary antinuclear antibodies (ANA) and tertiary lymphoid tissues (TLTs) using a preclinical mouse model. We observed that BAFF levels were elevated in smokers and mice exposed to cigarette smoke. In mice, BAFF expression was rapidly induced in the lungs following 4 days of cigarette smoke exposure and remained elevated following 8 and 24 weeks of exposure. Alveolar macrophages were the major source of BAFF Blockade of BAFF using a BAFF receptor-Fc (BAFFR-Fc) construct prevented pulmonary ANA and TLT formation when delivered concurrent with cigarette smoke exposure. Under these conditions, no impact on lung inflammation was observed. However, administration of BAFFR-Fc following smoking cessation markedly reduced the number of TLTs and ANA levels and, of note, reduced pulmonary neutrophilia. Altogether, this study shows for the first time a central role of BAFF in the induction and maintenance of cigarette smoke-induced pulmonary ANA and suggests that BAFF blockade following smoking cessation could have beneficial effects on persistent inflammatory processes.In this study, we assessed the expression of B-cell activating factor (BAFF) in smokers, and investigated the functional importance of BAFF in the induction and maintenance of cigarette smoke-induced pulmonary antinuclear antibodies (ANA) and tertiary lymphoid tissues (TLTs) using a preclinical mouse model. Data presented show that BAFF plays a central role in the induction and maintenance of cigarette smoke-induced pulmonary ANA and suggest a therapeutic potential for BAFF blockade in limiting autoimmune processes associated with smoking

Alterations in skeletal muscle cell homeostasis in a mouse model of cigarette smoke exposure.

Skeletal muscle dysfunction is common in chronic obstructive pulmonary disease (COPD), a disease mainly caused by chronic cigarette use. An important proportion of patients with COPD have decreased muscle mass, suggesting that chronic cigarette smoke exposure may interfere with skeletal muscle cellular equilibrium. Therefore, the main objective of this study was to investigate the kinetic of the effects that cigarette smoke exposure has on skeletal muscle cell signaling involved in protein homeostasis and to assess the reversibility of these effects.A mouse model of cigarette smoke exposure was used to assess skeletal muscle changes. BALB/c mice were exposed to cigarette smoke or room air for 8 weeks, 24 weeks or 24 weeks followed by 60 days of cessation. The gastrocnemius and soleus muscles were collected and the activation state of key mediators involved in protein synthesis and degradation was assessed.Gastrocnemius and soleus were smaller in mice exposed to cigarette smoke for 8 and 24 weeks compared to room air exposed animals. Pro-degradation proteins were induced at the mRNA level after 8 and 24 weeks. Twenty-four weeks of cigarette smoke exposure induced pro-degradation proteins and reduced Akt phosphorylation and glycogen synthase kinase-3β quantity. A 60-day smoking cessation period reversed the cell signaling alterations induced by cigarette smoke exposure.Repeated cigarette smoke exposure induces reversible muscle signaling alterations that are dependent on the duration of the cigarette smoke exposure. These results highlights a beneficial aspect associated with smoking cessation