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

• Grant number: 24/18328-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2025
• End date: April 30, 2026
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Aristides Tadeu Correia
• Grantee: Mariana Kasuga Morya
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

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