Serpınb1 Ve Serpınb2 Proteaz İnhibitörlerinin Bronş Epitel Hücrelerindeki İnflamatuvar Cevaptaki Rolü

Abstract

Asthma is a serious health problem affecting nearly 300 million people worldwide. Asthma frequency varies based on countries and even based on regions of same country. For example, Australia and New Zealand have a frequency of 10-25%, while Southeast Asian countries, North American Indians and Eskimos have a frequency of less than 1%. It is reported that frequency in European countries is between 5-10%, while that in Romania (1.5%) and Greece (1.9%) is relatively lower. The prevalence of asthma in Turkey is higher than the regional average. Studies conducted in our country have shown such a high prevalence that the frequency is between 0.7-14.8% in children and 0.3-7.6% in adults. Asthma is a chronic airway disease. It is characterized by bronchial contraction (narrowing), airway hyperreactivity and inflammation. Asthma has a complex structure which contains various phenotypic features and affected by genetic and environmental factors. The consensus on the pathophysiology of asthma is the disruption in the balance between epithelial tissue deconstruction and construction which causes airway remodelling. Allergens, airway irritants, chemicals and viral respiratory tract factors are initiative steps causing asthma. These factors lead to airway epitheliumdesquamation, inflammation, bronchial hyperresponsiveness, and airway contraction. The molecules that contribute to the development of this inflammatory response are cytokines, chemokines, lipid mediators and growth factors synthesized from epithelial cells. Epithelial cells are the first line defense cells that contact allergens in the airways and form a physical wall against harmful substances that come in through breathing. It plays an important role in the first step of airway defense by creating an inflammatory response with these secreted molecules. In addition to continuous breathing of toxins and oxidants, proteases also contribute to deterioration in integrity of the airway epithelium. Most of the allergens such as house dust mites, pollen, fungus, bacteria and viruses have protease activity. Against this destructive effect of proteases, epithelial cells synthesize protease inhibitors and preserve the protease-antiprotease balance. Which protease inhibitors are synthesized from epithelial cells after allergen contact and which metabolic pathways play a role during synthesis remain unclear. In this thesis study, role of serine protease inhibitor B1 (SERPINB1) and serine protease inhibitor B2 (SERPINB2) whose expressions are altered in bronchial epithelial cells after cysteine protease Dermatophagoides pteronyssinus 1 (Der p 1) exposure, in inflammatuar response and the effects of cytokines, chemokines, and growth factors in this response were investigated via real time polymerase chain reaction at RNA level and ELISA at protein level. For this purpose, SERPINB1 and SERPINB2 expressions were silenced by using gene-specific siRNA. SERPINB1 and SERPINB2 protease inhibitors were found to be effective on the expressions of IL-6, IL-8, RANTES, GM-CSF and TSLP inflammatory mediators.