Mezenkimal Kök Hücre Eksozomlarının Eozinofil İlişkili İnflamatuar Yanıtlar ve Epitel Bariyer Hasarı Üzerindeki Düzenleyici Etkilerinin İncelenmesi

Abstract

Barrier structure formed by epithelial cells in the lung, which is directly and continuously exposed to harmful factors taken by inhalation; plays a protective role against many factors such as allergens, pollutants, and pathogens. Lung epithelial barrier can be damaged due to increased inflammatory responses, disruption of cell-cell connections and excessive mucus production. In inflammatory conditions where eosinophils increase in the environment, many factors produced from eosinophils also play a role in damage. As a result of impaired barrier integrity, lungs become vulnerable to harmful factors and susceptibility to diseases increases. Therefore, regulation of inflammatory responses and improvement of barrier integrity is very important for barrier damage-related diseases. Mesenchymal stem cells (MSCs) have been used in the treatment of many inflammatory diseases due to their immunomodulation capacity and it has been shown that these cells can regulate unbalanced immune responses. However, over time, due to various side effects, there has been a trend towards MSC exosomes that mediate their immunomodulating properties. It has been shown that exosomes, which are 'cell-free' treatment options, can regulate immune responses like MSCs, but no study has been found that examines their effects on lung epithelial barrier damage.

Within the scope of the project, an epithelial barrier model was created using differentiated human lung epithelial cells, and then the established epithelial-eosinophil co-culture system was stimulated with lipopolysaccharide to create a barrier damage. In this model, damage-related molecules were examined at the gene and protein level, in addition, barrier integrity and cell junctions were analyzed. Then, these responses were examined in the presence of MSC exosomes, which show therapeutic potential due to their immunomodulation capacity, and the regulatory effects of exosomes on barrier damage were investigated. When the results were examined, it was revealed that exosome could regulate the levels of cytokine/chemokine and damage-related molecules such as IL-6, IL-8, MMP-9, TIMP-1, IL-33, TSLP, which play a role in lung epithelial barrier damage. MSC exosomes, which have been shown to affect the responses associated with excessive mucus production through MUC5AC gene expression; It has also been shown to play a role in the regulation of the impaired barrier integrity and the level of the tight junction molecule ZO-1.