Gene therapy for allergic diseases

Airway diseases such as allergic asthma and rhinitis are characterized by a T-helper type 2 (Th2) response. Treatment of allergic airway diseases is currently limited to drugs that relieve disease symptoms and inflammation. In the search for new therapeutics, efforts have been made to treat allergic airway disease with gene therapy, and many preclinical studies have demonstrated its impressive potential. Most strategies focus on blocking the expression of proinflammatory proteins or transcription factors involved in the disease pathogenesis using antisense oligonucleotides, DNAzymes, small interfering RNA, or blocking of microRNAs using antagomirs. Changing the Th1/Th2 balance by overexpressing Th1-stimulating factors is another treatment option. Although the proof of concept is convincing in animal models, progress in humans remains limited. In this review, we focus on preclinical models to describe the recent developments and major breakthroughs for treating allergic airway diseases with gene therapy

The role of the tachykinin NK1 receptor in airway changes in a mouse model of allergic asthma

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Role of tumor necrosis factor-α and its receptors in diesel exhaust particle-induced pulmonary inflammation

Inhalation of diesel exhaust particles (DEP) induces an inflammatory reaction in the lung. However, the underlying mechanisms remain to be elucidated. Tumor necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine that operates by binding to tumor necrosis factor receptor 1 (TNFR1) and tumor necrosis factor receptor 2 (TNFR2). The role of TNF-alpha signaling and the importance of either TNFR1 or TNFR2 in the DEP-induced inflammatory response has not yet been elucidated. TNF-alpha knockout (KO), TNFR1 KO, TNFR2 KO, TNFR1/TNFR2 double KO (TNFR-DKO) and wild type (WT) mice were intratracheally exposed to saline or DEP. Pro-inflammatory cells and cytokines were assessed in the bronchoalveolar lavage fluid (BALF). Exposure to DEP induced a dose-dependent inflammation in the BALF in WT mice. In addition, levels of TNF-alpha and its soluble receptors were increased upon exposure to DEP. The DEP-induced inflammation in the BALF was decreased in TNF-alpha KO, TNFR-DKO and TNFR2 KO mice. In contrast, the inflammatory response in the BALF of DEP-exposed TNFR1 KO mice was largely comparable with WT controls. In conclusion, these data provide evidence for a regulatory role of TNF-alpha in DEP-induced pulmonary inflammation and identify TNFR2 as the most important receptor in mediating these inflammatory effects

Endoscopic ultrasound reduces surgical mediastinal staging in lung cancer: A randomized trial

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