Allais Liesbeth, Kumar Smitha, Debusschere Karlijn, Verschuere Stephanie, Maes Tania, De Smet Rebecca, Conickx Griet, De Vos Martine, Laukens Debby, Joos Guy F, Brusselle Guy G, Elewaut Dirk, Cuvelier Claude A, Bracke Ken R
Department of Medical and Forensic Pathology, Ghent University, Ghent, Belgium.
Laboratory for Translational Research in Obstructive Pulmonary diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
PLoS One. 2015 Nov 2;10(11):e0141570. doi: 10.1371/journal.pone.0141570. eCollection 2015.
The inflammatory cytokine TNF-α is a central mediator in many immune-mediated diseases, such as Crohn's disease (CD), spondyloarthritis (SpA) and chronic obstructive pulmonary disease (COPD). Epidemiologic studies have shown that cigarette smoking (CS) is a prominent common risk factor in these TNF-dependent diseases. We exposed TNFΔARE mice; in which a systemic TNF-α overexpression leads to the development of inflammation; to 2 or 4 weeks of air or CS. We investigated the effect of deregulated TNF expression on CS-induced pulmonary inflammation and the effect of CS exposure on the initiation and progression of gut and joint inflammation. Upon 2 weeks of CS exposure, inflammation in lungs of TNFΔARE mice was significantly aggravated. However, upon 4 weeks of CS-exposure, this aggravation was no longer observed. TNFΔARE mice have no increases in CD4+ and CD8+ T cells and a diminished neutrophil response in the lungs after 4 weeks of CS exposure. In the gut and joints of TNFΔARE mice, 2 or 4 weeks of CS exposure did not modulate the development of inflammation. In conclusion, CS exposure does not modulate gut and joint inflammation in TNFΔARE mice. The lung responses towards CS in TNFΔARE mice however depend on the duration of CS exposure.
炎症细胞因子肿瘤坏死因子-α（TNF-α）是许多免疫介导疾病的核心介质，如克罗恩病（CD）、脊柱关节炎（SpA）和慢性阻塞性肺疾病（COPD）。流行病学研究表明，吸烟（CS）是这些TNF依赖性疾病的一个突出的共同危险因素。我们将TNFΔARE小鼠（其中全身性TNF-α过表达会导致炎症发展）暴露于空气或香烟烟雾中2周或4周。我们研究了TNF表达失调对香烟烟雾诱导的肺部炎症的影响，以及香烟烟雾暴露对肠道和关节炎症的起始和进展的影响。在暴露于香烟烟雾2周后，TNFΔARE小鼠肺部的炎症明显加重。然而，在暴露于香烟烟雾4周后，这种加重情况不再出现。在暴露于香烟烟雾4周后，TNFΔARE小鼠肺部的CD4+和CD8+T细胞没有增加，中性粒细胞反应减弱。在TNFΔARE小鼠的肠道和关节中，暴露于香烟烟雾2周或4周并未调节炎症的发展。总之，暴露于香烟烟雾不会调节TNFΔARE小鼠的肠道和关节炎症。然而，TNFΔARE小鼠对香烟烟雾的肺部反应取决于香烟烟雾暴露的持续时间。
