DER P 6 ve CUP A 1 Alerjenlerine Maruziyet Sonucunda Nazal ve Bronşiyal Epitel Hücre Cevabı ve Eozinofillerin Bu Cevaba Katkısı

Abstract

Nowadays, the prevalence of allergic diseases is increasing and it is considered as the epidemic of the twenty-first century. Especially asthma, which affects 300 million people worldwide, and allergic rhinitis, which is seen in 400 million people, are among these diseases. Allergic rhinitis is observed in most individuals with asthma, and these two diseases are related to each other. In addition to its molecular mechanisms, it shows similarity in environmental factors that trigger the disease. Pollens and house dust mites are the most common aeroallergens to which epithelial cells, the first line of defense in the lower and upper respiratory tracts, are exposed. Pollens, which are included in the class of exogenous aeroallergens, cause seasonal allergies, but plants planted outside the natural habitat for landscaping can trigger allergies in patients. Especially in Turkey and Mediterranean countries, the Arizona cypress planted as an ornamental plant in parks, gardens and roadsides has the capacity to produce 123 billion pollen and its major allergen is defined as Cup a1. House dust mite, which is one of the household aeroallergens, is constantly exposed to and causes damage to epithelial cells with its allergens with protease activity. Dermatophagoides ptrenoysinuss is one of the most common house dust mite species in studies. Although Der p1 and Der p2 are known as major allergens of this mite, it has been reported that Der p6 allergen, which has serine protease activity, may be major in some studies.

In nasal and bronchial epithelial cells exposed to environmental allergens, both cell death can be observed, and cells can lose their epithelial character and gain mesenchymal character. Eosinophils, which play an important role in the pathophysiology of both allergic asthma and allergic rhinitis, can affect cell responses when they migrate to the inflammation area and become activated. Within the scope of the thesis study, nasal and bronchial epithelial cells were stimulated by Cup a1 and Der p6 allergens, which have limited information in the literature, and cell responses were determined by caspase-dependent & independent (apoptosis, anoikis, necroptosis, parthanatos) cell death pathways and epithelial mesenchymal transformation (EMT) at the level of gene expression. The first stage of the experiments was carried out in monolayer culture and the appropriate concentration & time was determined. Afterwards, epithelial cells were grown by the ALI-culture process and co-cultured with activated eosinophils. Mono and co-culture groups formed at the end of the ALI-culture process were stimulated with appropriate allergen conditions and cell responses were investigated again through death pathways and EMT. The synergistic effects of allergens on cells were determined by performing allergen stimulations separately and together.

When the results obtained were evaluated, it was determined that more death was observed in bronchial epithelial cells compared to nasal epithelial cells after allergen stimulation and bronchial epithelial cells formed cell responses later. It was determined that Der p6 allergen triggered programmed death pathways in bronchial epithelial cells, but high dose Cup a1 allergen caused necrosis in the cell. In nasal epithelial cells, it was observed that the cell response to both allergens was through programmed death pathways. It was understood that epithelial cells of different origins gave different responses to allergens in monolayer culture stimulation. When the gene expression results obtained from mono and co-culture were compared, it was determined that eosinophils affected the cell response. The results obtained with Cup a1 and Der p6 allergens will contribute to the literature and will be a pioneer for further studies.