Cigarette smoke differentially affects IL-13-induced gene expression in human airway epithelial cells

Abstract

Allergic airways inflammation in asthma is characterized by an airway epithelial gene signature composed of POSTN,CLCA1, and SERPINB2. This Th2 gene signature is proposed as a tool to classify patients with asthma into Th2‐high and Th2‐low phenotypes. However, many asthmatics smoke and the effects of cigarette smoke exposure on the epithelial Th2 gene signature are largely unknown. Therefore, we investigated the combined effect of IL‐13 and whole cigarette smoke (CS) on the Th2 gene signature and the mucin‐related genes MUC5AC and SPDEF in air–liquid interface differentiated human bronchial (ALI‐PBEC) and tracheal epithelial cells (ALI‐PTEC). Cultures were exposed to IL‐13 for 14 days followed by 5 days of IL‐13 with CS exposure. Alternatively, cultures were exposed once daily to CS for 14 days, followed by 5 days CS with IL‐13. POSTN,SERPINB2, and CLCA1 expression were measured 24 h after the last exposure to CS and IL‐13. In both models POSTN,SERPINB2, and CLCA1 expression were increased by IL‐13. CS markedly affected the IL‐13‐induced Th2 gene signature as indicated by a reduced POSTN,CLCA1, and MUC5AC expression in both models. In contrast, IL‐13‐induced SERPINB2 expression remained unaffected by CS, whereas SPDEF expression was additively increased. Importantly, cessation of CS exposure failed to restore IL‐13‐induced POSTN and CLCA1 expression. We show for the first time that CS differentially affects the IL‐13‐induced gene signature for Th2‐high asthma. These findings provide novel insights into the interaction between Th2 inflammation and cigarette smoke that is important for asthma pathogenesis and biomarker‐guided therapy in asthma.

Serum Periostin Is Negatively Correlated With Exposure to Formaldehyde and Volatile Organic Compounds in Children

“…Short-term exposure to cigarette smoke has been found to induce a Th2 inflammatory response, increasing the concentration of IL-13 and differentially affecting the IL-13-induced expression profile, including the marked down-regulation of periostin ( POSTN ) gene expression, as in Th2-high phenotype asthma. 17 In addition, an epidemiological study showed that chronic exposure to high levels of VOCs was significantly associated with reduced serum IL-13 concentrations. 18 …”

Age and early maternal smoking contribute to epithelial cell IL‐13 responsiveness in a pediatric asthma population

“…1 Basophils also express IL-5Rα, participate in T2-mediated inflammatory pathways 2 and have been associated with exacerbation frequency. [5][6][7][8] Our primary objective was to determine whether anti-IL-5 monoclonal antibody treatment reduces blood basophil levels as an additional potential efficacy mechanism. [5][6][7][8] Our primary objective was to determine whether anti-IL-5 monoclonal antibody treatment reduces blood basophil levels as an additional potential efficacy mechanism.…”

“…Following Cincinnati Children's Hospital Medical Center (CCHMC) IRB approval, children (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) years old) with physician-diagnosed asthma were enrolled in the Pediatric Environmental Exposure Study (PEES). 4 Children and parents completed surveys to assess current secondhand smoke (SHS) exposure, early maternal smoking, asthma symptom frequency over the past 4 weeks (wheeze, shortness of breath, cough, and chest tightness), asthma control (childhood Asthma Control Test [ACT]), medication usage/treatment step, and exposure to air pollutants based on estimated mean concentration of elemental carbon attributable to traffic (ECAT) exposure using birth and current address.…”

“…5 Similarly, maternal smoking during pregnancy is associated with persistent asthma in children with specific IL-13 SNPs, 6 and cigarette smoke exposures alter IL-13-induced gene expression in human epithelial cells. 7 The mechanisms related to this effect remain unclear, but may involve epigenetics as smoke exposure induces epithelial cell epigenetic changes. Importantly, methylation of CpG sites in the IL-4Rα promoter has been linked to altered asthma risk, although it is unclear whether such effects are related to altered IL-13 production, altered IL-13 responsiveness, or other poorly appreciated influences.…”

“…3 Whilst basophil progenitors are unlikely to depend on IL-5 for development, 4 blood basophil counts measured in routine clinical laboratories suggest they decrease following mepolizumab treatment. [5][6][7][8] Our primary objective was to determine whether anti-IL-5 monoclonal antibody treatment reduces blood basophil levels as an additional potential efficacy mechanism. To achieve this, we measured blood basophils, eosinophils and other type 2 inflammatory cells, before and after 16 weeks of mepolizumab ("Nucala," GlaxoSmithKline) by flow cytometry.…”