Hava Yolu Epitel Hücrelerinde Dektin-1 Reseptörlerin Rolü

Abstract

Asthma is a chronic inflammatory disease of the airway that affects people of all ages and genders, although it is more common in childhood. In our era, when industry and urbanization are rapidly increasing, the asthma prevalence is rising. Genetic and environmental factors play a role in the initiation and development of the disease. Non-allergenic environmental factors such as cigarette smoke, dietary habits, air pollution, as well as allergic factors such as house dust mites, pollens, and fungi have been associated with the onset, development, and severity of asthma in individuals sensitive to such allergens. Fungi, which we frequently encounter in our natural environment and are especially resistant to climate changes, can cause severe respiratory disorders in individuals with fungal sensitivity. It has been shown in clinical studies that Aspergillus fumigatus species of fungi, which are among the temperature-resistant fungi (thermotolerant) and have high pathogenicity, play a primary role in Severe Asthma with Fungal Sensitization (SAFS) and Allergic Bronchopulmonary Aspergillosis (ABPA) diseases. This species of fungus, which locates in the respiratory tract through its tiny spores, contributes to epithelial cell damage and inflammation with the protease enzymes it secretes. Except for the protease activities of these fungi, there is literature information that their structures, such as β-glucan and chitin in the cell wall, are also effective in inflammation. Although β-glucan, which is the main component of the fungal cell wall, is recognized by scavenger receptors and complementary receptor 3, its main receptor is Dectin-1. The Dectin-1 receptor, in the Type II membrane protein group of the C-type lectin-like receptor family, was first discovered in murine dendritic cells. In later studies, it was shown that this receptor is found in inflammatory cells such as leukocytes, macrophages, neutrophils and T cells as well as structural cells such as epithelial cells. Within the scope of the thesis study, Dectin-1 receptor expression in BEAS-2B cells stimulated with β-glucan obtained from Aspergillus fumigatus species was investigated at the level of RNA and protein. The effect of β-glucan stimulation on Dectin-1 expression in the presence of Th2 type cytokine (IL4+IL13) was investigated. Additionally, to determine the pro-inflammatory and anti-inflammatory cytokine and chemokine profile in cells stimulated by β-glucan in our study, expressions of IL-6, IL-8, Rantes, IL-25, IL-33, and TSLP cytokines and chemokines were investigated at the RNA level by Real-time Polymerase Chain Reaction (PCR) method. In the thesis study, it was found that Dectin-1 expression increased in cells stimulated with β-glucan extracted from Aspergillus fumigatus. Besides, it was detected that this increase was further increased in the presence of IL-4 and IL-13, which are Th2 type cytokines. It was observed that the presence of Dectin-1 increased in stimulation with Th2 type cytokines in both Western Blot and immunofluorescent stain results at the protein level. In the thesis study, changes in the expression of epithelial cell-derived cytokines were investigated in the presence of only β-glucan. As a result of stimulation with β-glucan, an increase in IL-6 and IL-25 gene expressions and decreased IL-8 gene expression were found compared to the control group. It has been found that exposure to high doses of β-glucan increases RANTES expression.