ABSTRACT
Macrolides have anti-inflammatory and immunomodulatory effects and have been used to treat patients with several inflammatory diseases, including diffuse panbronchiolitis (DPB), cystic fibrosis, bronchiectasis, chronic obstructive pulmonary disease and chronic rhinosinusitis. Macrolide therapy improves symptoms and respiratory function, prevents exacerbation of these diseases and increases the survival rate in patients with DPB. Macrolides reduce mucus production in the airways and nasal cavity, inhibit neutrophil chemotaxis and survival, and reduce the production of cytokines, such as interleukin-8, and intercellular adhesion molecule, which activates neutrophil extravasation and migration at sites of chronic inflammation and rhinovirus (RV) attachment to airway epithelial cells. Macrolides also have antibacterial effects, including inhibition of virulence factor production, Pseudomonas adhesion, biofilm formation and quorum-sensing mechanisms that activate bacterial violence. Additionally, macrolides reduce cytokine production in airway epithelial cells after viral infection and decrease the replication of respiratory viruses, including RV, influenza virus and respiratory syncytial virus. These effects are mediated through several mechanisms, including inhibiting nuclear factor kappa-B (NF-kB) activity, the p44/42 mitogen-activated protein kinase (p44/42 MAPK) pathway and chloride channel-mediated water secretion and reducing the number of acidic endosomes where viral RNA from RVs, influenza viruses or coronaviruses enters the cytoplasm. Here, we introduce the antiviral and immunomodulatory effects of macrolides and the associated mechanisms in the human airway and lung cells. © 2021 Nova Science Publishers, Inc.
ABSTRACT
The recent global pandemic of Corona Virus Disease-19 has impacted all aspects of society, producing a growing demand for a powerful virus inactivation method. To assess a potential and mechanism of human coronavirus inactivation using atmospheric pressure plasma (APP) technology, replication of a human coronavirus (HCoV-229E) after He + H2O APP plume exposure was evaluated using rhesus monkey kidney epithelial cells. The HCoV-229E titers were reduced by 3 log(10)TCID(50) after the APP exposure for 30 s, showing a strong virus-inactivation efficacy of the APP. It was experimentally verified that the APP produced the liquid-phase reactive oxygen and nitrogen species (RONS) at high rates [e.g. (OH)-O-center dot: similar to 1.7 nmol s(-1), H2O2 (including H2O2 precursors): similar to 9.2 nmol s(-1), NO2 (-) (including NO2 (-) precursors): similar to 3.3 nmol s(-1)]. However, an administration of H2O2 with NO2 (-) failed to inactivate the virus and only Mn type superoxide dismutase among several RONS scavengers for (OH)-O-center dot, HO2 (center dot)/O-2 O-center dot-, 1(2), and (NO)-N-center dot/(NO2)-N-center dot was significantly effective for the recovery of the APP-induced decrease in the viral titers. This suggests O-2 (center dot-)-related chemical reaction in a network of interconnected reactions induced by the APP exposure is very important for the APP-induced virus inactivation. These results provide new insight into a more efficient inactivation method of human coronavirus using APPs.