Transcriptomic Analysis Reveals Priming of The Host Antiviral Interferon Signaling Pathway by Bronchobini® Resulting in Balanced Immune Response to Rhinovirus Infection in Mouse Lung Tissue Slices

Rhinovirus (RV) is the predominant virus causing respiratory tract infections. Bronchobini® is a low dose multi component, multi target preparation used to treat inflammatory respiratory diseases such as the common cold, described to ease severity of symptoms such as cough and viscous mucus production. The aim of the study was to assess the efficacy of Bronchobini® in RV infection and to elucidate its mode of action. Therefore, Bronchobini®’s ingredients (BRO) were assessed in an ex vivo model of RV infection using mouse precision-cut lung slices, an organotypic tissue capable to reflect the host immune response to RV infection. Cytokine profiles were assessed using enzyme-linked immunosorbent assay (ELISA) and mesoscale discovery (MSD). Gene expression analysis was performed using Affymetrix microarrays and ingenuity pathway analysis. BRO treatment resulted in the significant suppression of RV-induced antiviral and pro-inflammatory cytokine release. Transcriptome analysis revealed a multifactorial mode of action of BRO, with a strong inhibition of the RV-induced pro-inflammatory and antiviral host response mediated by nuclear factor kappa B (NFkB) and interferon signaling pathways. Interestingly, this was due to priming of these pathways in the absence of virus. Overall, BRO exerted its beneficial anti-inflammatory effect by priming the antiviral host response resulting in a reduced inflammatory response to RV infection, thereby balancing an otherwise excessive inflammatory response

Cigarette smoke induced pathophysiological changes in the extracellular matrix but not inflammation as early events in fresh human lung tissue

Cigarette smoke (Cs) inhalation is a main reason to develop chronic obstructive pulmonary disease (COPD), characterised by degradation of alveoli, mucus hypersecretion, emphysema development and inflammation [1]. The pathophysiology of COPD is not well understood so the mechanisms that underlie various components of COPD need to be modelled in vitro, specifically using Cs. We assessed the pathophysiological effects of Cs and Cs condensate (Csc) on fresh human lung tissue. Human Precision Cut Lung Slices (PCLS) were exposed to Csc submerged or whole Cs in an Air-Liquid Interface using the in vitro exposure device P.R.I.T.® ExpoCube®. Cytotoxicity, release of cytokines and extracellular matrix (ECM) proteins were measured and gene expression analysis upon RNA isolation from PCLS was performed. PCLS exposed to Csc or Cs showed concentration-dependent loss of tissue viability. Gene expression analysis upon RNA isolated from lung tissue exposed to nontoxic doses of Csc of literature-based COPD-relevant genes indicate damage of epithelium by upregulation of genes involved in tissue injury (e.g. mmp) and specific metabolic activity (e.g. cyp1a1). Samples exposed to control substance LPS did not show increased expression in emphysema associated genes but in genes indicating inflammation (e.g. il-6). These data can be supported by increased production of proteins related to the extracellular matrix (e.g. MMP9, RAGE) and inhibited expression in pro-inflammatory cytokines after Cs exposure in an air-liquid culture. Supportive results were presented in BAL samples from COPD subjects showing markers of apoptosis [2]. These results indicate that early stages of Cs induced lung tissue changes are primarily not provoked by immunological processes but by apoptosis, increased specific metabolic activity and damage of the epithelium. [1] Hodge, S. et al. (2005). ERJ 25 (3), S. 447-454. [2] Shaykhiev, R.; Crystal, R. (2014). AnnalsATS 11 Suppl 5, S252-8

The Political Viability of Carbon Pricing: Policy Design and Framing in British Columbia and California

The adoption of climate policies with visible, substantial costs for households is uncommon because of expected political backlash, but British Columbia\u27s carbon tax and California\u27s cap-and-trade program imposed such costs and still survived vigorous opposition. To explain these outcomes, this paper tests hypotheses concerning policy design, framing, energy prices, and elections. It conducts universalizing and variation-finding comparisons across three subcases in the two jurisdictions and uses primary sources to carry out process tracing involving mechanisms of public opinion and elite position taking. The paper finds strong support for the timing of independent energy price changes, exogenous causes of election results, reducing the visibility of carbon pricing, and using public-benefit justifications, as well as some support for making concessions to voters. By contrast, the effects of the use of revenue, industry exemptions/compensations, and making polluters pay are not uniform, because the former depends on how it is embedded in coalition building efforts and a middle path between exempting or compensating industry and burdening it appears to be more effective than pursuing just one or the other approach