N-acetyl-l-cysteine (NAC) inhibits virus replication and expression of pro-inflammatory molecules in A549 cells infected with highly pathogenic H5N1 influenza A virus

Abstract

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 The combination of BAY 11-7085 and SB203580 resulted in increased inhibitory effects on virus replication and production of pro-inflammatory molecules relative to either single treatment. NAC inhibits H5N1 replication and H5N1-induced production of proinflammatory molecules. Therefore, antioxidants like NAC represent a potential additional treatment option that could be considered in the case of an influenza A virus pandemic.

N-acetyl-l-cysteine (NAC) inhibit mucin synthesis and pro-inflammatory mediators in alveolar type II epithelial cells infected with influenza virus A and B and with respiratory syncytial virus (RSV)

“…In our model, NAC blocked the induction of both cytokines at the dose of 10 mM at the expression and at the release level. These results are in line with those recently published by Geiler et al [20] in an in vitro model of influenza A infection in A549. Similar effects of NAC for IL8 release in A549 after RSV infection have been reported [16].…”

“…We observed a strong induction of TNF-alpha expression and release after virus infection that was significant inhibited in NAC 10 mM pre-treated cultures, in line with previously reported results [16,20].…”

“…Elevation of mitochondrial superoxide increases susceptibility to influenza infection in mice [18] and in A549 [19]. ROS induction after influenza infection increases the expression of pro-inflammatory molecules like IL8, IL6, CCL5 or CXCL10 [20]. These effects have been associated with the activation of NFSputum volume and virulence are one of the main symptoms related to exacerbations [2].…”

“…This molecule reduces the number A c c e p t e d M a n u s c r i p t 5 and impact of COPD exacerbations [28] and also the inflammatory response in epithelial cells exposed to H5N1 influenza A virus [20]. Although anti-mucolitic effects of NAC are well established, little is known about its effects on the MUC5AC expression in virus models of infection.…”

Antioxidant Therapy as a Potential Approach to Severe Influenza-Associated Complications

“…Figure 3), the acetylated derivative of the amino acid L-cysteine, is an excellent source of thiol groups, and is converted in the body into metabolites capable of stimulating glutathione synthesis, promoting detoxification, and acting directly as free radical scavengers [45]. NAC inhibited the induction of apoptosis [46][47][48] and gene expression for pro-inflammatory cytokines and chemokines such as IL-6, IL-8, RANTES and interferon-inducing protein (IP)-10, by influenza virus infection [48]. NAC inhibited the proliferation of influenza virus at an early, but not later, stage of infection [47,48].…”