Effects of calcineurin inhibitors (CsA,FK506) on MUC5AC and MUC5B mucins production in human tracheobronchial cells

• Grant number: 20/08384-6
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2022
• End date: December 31, 2024
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Rogerio Pazetti
• Grantee: Rogerio Pazetti
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Aristides Tadeu Correia
• Associated scholarship(s): 22/11416-2 - Establishment and maintenance of human tracheobronchial cell culture to study the action of immunosuppressive drugs on signaling pathways for the production of mucins from respiratory mucus., BP.TT

Abstract

Lung transplantation is the only treatment option for patients with terminal lung diseases. However, mortality and morbidity resulting from bronchial, infectious and graft rejection complications remain high. Possible reasons for such a high incidence of infectious complications include an allograft that is continuously exposed to the environment, problems with bronchial anastomosis and dysfunction of the mucociliary epithelium with impaired airway clearance. Experimental work carried out in our laboratory showed that some immunosuppressants used in lung transplantation caused adverse effects on the tracheobronchial mucociliary system, altering the ciliary beat rate and the quality of the mucus produced. Other studies, using lymphocytes, endothelial cells and smooth muscle cells, showed the interference of these immunosuppressants in some intracellular gene activation routes, which are the same present in the airway cells responsible for the production of MUC5AC and MUC5B mucins, which make up the respiratory mucus. Our hypothesis is that calcineurin-inhibiting drugs may interfere with mucus production routes and compromise the proper functioning of the airway mucociliary system. Thus, understanding the possible changes in the mucociliary system related to the isolated use of immunosuppressants may improve the therapeutic actions to prevent infectious complications in lung transplant patients. (AU)