Figure 5.

CO beneficial effects in cystic fibrosis (CF). CO may have several beneficial effects in CF. In addition to transcriptional induction of HO-1, CO helps to rebalance ion transport in bronchial epithelial cells by modulating the activity of BK_Ca channels, ENaC, and, possibly, CFTR. It has direct bactericidal activity and also primes the macrophages. It thus improves the host defense mechanisms by modulating autophagy, phagocytosis, the inflammasome, and immunometabolic responses. CO reduces cellular oxidative stress and improves cell survival by activating/inducing NO, GSH, NADPH, HO-1, PI3K/AKT, and Nrf2. CO also decreases hyper-inflammation by increasing levels of anti-inflammatory mediators, HO-1 and SPMs.