OBJECTIVE AND DESIGN: The exacerbate inflammatory response contributes to the progressive loss of lung function in cystic fibrosis (CF), a genetic disease that affects the osmotic balance of mucus and mucociliary clearance, resulting in a microenvironment that favors infection and inflammation. The purinergic system, an extracellular signaling pathway characterized by nucleotides, enzymes and receptors, may have a protective role in the disease, through its action in airway surface liquid (ASL) and anti-inflammatory response. MATERIALS AND METHODS: To make up this review, studies covering topics of CF, inflammation, ASL and purinergic system were selected from the main medical databases, such as Pubmed and ScienceDirect. CONCLUSION: We propose several ways to modulate the purinergic system as a potential therapy for CF, like inhibition of P2X7, activation of P2Y2, A2A and A2B receptors and blocking of adenosine deaminase. Among them, we postulate that the most suitable strategy is to block the action of adenosine deaminase, which culminates in the increase of Ado levels that presents anti-inflammatory actions and improves mucociliary clearance. Furthermore, it is possible to maintain the physiological levels of ATP to control the hydration of ASL. These therapies could correct the main mechanisms that contribute to the progression of CF.
OBJECTIVE AND DESIGN: The exacerbate inflammatory response contributes to the progressive loss of lung function in cystic fibrosis (CF), a genetic disease that affects the osmotic balance of mucus and mucociliary clearance, resulting in a microenvironment that favors infection and inflammation. The purinergic system, an extracellular signaling pathway characterized by nucleotides, enzymes and receptors, may have a protective role in the disease, through its action in airway surface liquid (ASL) and anti-inflammatory response. MATERIALS AND METHODS: To make up this review, studies covering topics of CF, inflammation, ASL and purinergic system were selected from the main medical databases, such as Pubmed and ScienceDirect. CONCLUSION: We propose several ways to modulate the purinergic system as a potential therapy for CF, like inhibition of P2X7, activation of P2Y2, A2A and A2B receptors and blocking of adenosine deaminase. Among them, we postulate that the most suitable strategy is to block the action of adenosine deaminase, which culminates in the increase of Ado levels that presents anti-inflammatory actions and improves mucociliary clearance. Furthermore, it is possible to maintain the physiological levels of ATP to control the hydration of ASL. These therapies could correct the main mechanisms that contribute to the progression of CF.
Authors: Scott C Bell; Marcus A Mall; Hector Gutierrez; Milan Macek; Susan Madge; Jane C Davies; Pierre-Régis Burgel; Elizabeth Tullis; Claudio Castaños; Carlo Castellani; Catherine A Byrnes; Fiona Cathcart; Sanjay H Chotirmall; Rebecca Cosgriff; Irmgard Eichler; Isabelle Fajac; Christopher H Goss; Pavel Drevinek; Philip M Farrell; Anna M Gravelle; Trudy Havermans; Nicole Mayer-Hamblett; Nataliya Kashirskaya; Eitan Kerem; Joseph L Mathew; Edward F McKone; Lutz Naehrlich; Samya Z Nasr; Gabriela R Oates; Ciaran O'Neill; Ulrike Pypops; Karen S Raraigh; Steven M Rowe; Kevin W Southern; Sheila Sivam; Anne L Stephenson; Marco Zampoli; Felix Ratjen Journal: Lancet Respir Med Date: 2019-09-27 Impact factor: 30.700
Authors: Fernanda Dos Anjos; Jonatha Wruck; Thiago Inácio Teixeira do Carmo; Victor Emanuel Miranda Soares; Débora Tavares de Resende E Silva; Margarete Dulce Bagatini; Sarah Franco Vieira de Oliveira Maciel Journal: Clin Med Res Date: 2022-02-07
Authors: Mazen Shihan; Tatyana Novoyatleva; Thilo Lehmeyer; Akylbek Sydykov; Ralph T Schermuly Journal: Int J Environ Res Public Health Date: 2021-10-20 Impact factor: 3.390