Pathogenesis of allergic airway inflammation

Center for Clinical and Translational Science, Creighton University School of Medicine, CRISS II, Room 510, Omaha, NE 68178, USA.
Current Allergy and Asthma Reports (Impact Factor: 2.45). 01/2010; 10(1):39-48. DOI: 10.1007/s11882-009-0081-7
Source: PubMed

ABSTRACT Advances have been made in defining the mechanisms for the control of allergic airway inflammation in response to inhaled antigens. Several genes, including ADAM33, DPP10, PHF11, GPRA, TIM-1, PDE4D, OPN3, and ORMDL3, have been implicated in the pathogenesis and susceptibility to atopy and asthma. Growing evidence associates asthma with a systemic propensity for allergic T-helper type 2 cytokines. Disordered coagulation and fibrinolysis also exacerbate asthma symptoms. Balance among functionally distinct dendritic cell subsets contributes to the outcome of T-cell-mediated immunity. Allergen-specific T-regulatory cells play a pivotal role in the development of tolerance to allergens and immune suppression. The major emphasis on immunotherapy for asthma during the past decade has been to direct the immune response to a type 1 response, or immune tolerance. In this review, we discuss the current information on the pathogenesis of allergic airway inflammation and potential immunotherapy, which could be beneficial in the treatment of airway inflammation, allergy, and asthma.

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    • "Under conditions of chronic inflammation in allergic asthma, neutrophils along with eosinophils are the first cells to be recruited to inflammatory sites (Baggiolini, 1998; Agrawal and Shao, 2010). Neutrophils, which are the most abundant leukocytes in the blood, use two basic strategies to eliminate microorganisms (Guimaraes- Costa et al., 2012). "
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    ABSTRACT: Asthma is frequently caused and/or exacerbated by sensitization to fungal allergens, which are ubiquitous in many indoor and outdoor environments. Severe asthma with fungal sensitization is characterized by airway hyperresponsiveness and bronchial constriction in response to an inhaled allergen that is worsened by environmental exposure to airborne fungi and which leads to a disease course that is often very difficult to treat with standard asthma therapies. As a result of complex interactions among inflammatory cells, structural cells, and the intercellular matrix of the allergic lung, patients with sensitization to fungal allergens may experience a greater degree of airway wall remodeling and progressive, accumulated pulmonary dysfunction as part of the disease sequela. From their development in the bone marrow to their recruitment to the lung via chemokine and cytokine networks, eosinophils form an important component of the inflammatory milieu that is associated with this syndrome. Eosinophils are recognized as complex multi-factorial leukocytes with diverse functions in the context of allergic fungal asthma. In this review, we will consider recent advances in our understanding of the molecular mechanisms that are associated with eosinophil development and migration to the allergic lung in response to fungal inhalation, along with the eosinophil's function in the immune response to and the immunopathology attributed to fungus-associated allergic pulmonary disease.
    Frontiers in Pharmacology 02/2013; 4:8. DOI:10.3389/fphar.2013.00008 · 3.80 Impact Factor
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    • "They are more prevalent in the lesions of both human and ApoE −/− mice suggesting that atherosclerosis is a Th1-dominant disease [20] [21]. Th2 cells are involved in allergic diseases such as atopic allergy and asthma [22]. Their role in atherosclerosis seems to depend on the stage and site of the disease. "
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    ABSTRACT: Atherosclerosis, the underlying cause of cardiovascular disease, is characterized by chronic inflammation and altered immune response. Cholesterol is a well-known risk factor associated with the development of cardiovascular diseases. Elevated serum cholesterol is unique because it can lead to development of atherosclerosis in animals and humans even in the absence of other risk factors. Modifications of low-density lipoproteins mediated by oxidation, enzymatic degradation, and aggregation result in changes in their function and activate both innate and adaptive immune system. Oxidized low-density lipoprotein (LDL) has been identified as one of the most important autoantigens in atherosclerosis. This escape from self-tolerance is dependent on the formation of oxidized phospholipids. The emerging understanding of the importance of immune responses against oxidized LDL in atherosclerosis has focused attention on the possibility of development of novel therapy for atherosclerosis. This review provides an overview of immune response to lipoproteins and the fascinating possibility of developing an immunomodulatory therapy for atherosclerosis.
    Cholesterol 08/2012; 12. DOI:10.1155/2012/571846
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    • "The pathogenesis of the allergic inflammation involves multiple mediators, cell types, and pathways [2]. Although the skewing of Th2 cytokines is considered the key pathogenic factor for asthma [3], oxidative stress may also be a crucial contributor to asthma development. Accumulating evidence demonstrates that levels of oxidative stress are increased both in children and in adults with asthma, not only in their lungs but also in the blood [4]. "
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    ABSTRACT: 8-Oxoguanine-DNA glycosylase (OGG-1) is a base excision DNA repair enzyme; however, its function in modulating allergic diseases remains undefined. Using OGG-1 knockout (KO) mice, we show that this protein affects allergic airway inflammation after sensitization and challenge by ovalbumin(OVA). OGG-1 KO mice exhibited less inflammatory cell infiltration and reduced oxidative stress in the lungs after OVA challenge compared to WT mice. The KO phenotype included decreased IL-4, IL-6, IL-10, and IL-17 in lung tissues. In addition, OGG-1 KO mice showed decreased expression and phosphorylation of STAT6 as well as NF-κB. Down-regulation of OGG-1 by siRNA lowered ROS and IL-4 levels but increased IFN-γ production in cultured epithelial cells after exposure to house dust mite extracts. OGG-1 may affect the levels of oxidative stress and proinflammatory cytokines during asthmatic conditions. OGG-1 deficiency negatively regulates allergen-induced airway inflammatory response.
    Free Radical Biology and Medicine 11/2011; 52(2):392-401. DOI:10.1016/j.freeradbiomed.2011.10.490 · 5.71 Impact Factor
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