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
The antioxidant N-acetyl-l-cysteine (NAC) had been shown to inhibit replication of seasonal human influenza A viruses. Here, the effects of NAC on virus replication, virus-induced pro-inflammatory responses and virus-induced apoptosis were investigated in H5N1-infected lung epithelial (A549) cells....
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| Veröffentlicht in: | Biochemical pharmacology 2010-02, Vol.79 (3), p.413-420 |
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| creator | Geiler, Janina Michaelis, Martin Naczk, Patrizia Leutz, Anke Langer, Klaus Doerr, Hans-Wilhelm Cinatl, Jindrich |
| description | The antioxidant N-acetyl-l-cysteine (NAC) had been shown to inhibit replication of seasonal human influenza A viruses. Here, the effects of NAC on virus replication, virus-induced pro-inflammatory responses and virus-induced apoptosis were investigated in H5N1-infected lung epithelial (A549) cells. NAC at concentrations ranging from 5 to 15mM reduced H5N1-induced cytopathogenic effects (CPEs), virus-induced apoptosis and infectious viral yields 24h post-infection. NAC also decreased the production of pro-inflammatory molecules (CXCL8, CXCL10, CCL5 and interleukin-6 (IL-6)) in H5N1-infected A549 cells and reduced monocyte migration towards supernatants of H5N1-infected A549 cells. The antiviral and anti-inflammatory mechanisms of NAC included inhibition of activation of oxidant sensitive pathways including transcription factor NF-κB and mitogen activated protein kinase p38. Pharmacological inhibitors of NF-κB (BAY 11-7085) or p38 (SB203580) exerted similar effects like those determined for NAC in H5N1-infected cells. 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 pro-inflammatory molecules. Therefore, antioxidants like NAC represent a potential additional treatment option that could be considered in the case of an influenza A virus pandemic. |
| doi_str_mv | 10.1016/j.bcp.2009.08.025 |
| format | Article |
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Here, the effects of NAC on virus replication, virus-induced pro-inflammatory responses and virus-induced apoptosis were investigated in H5N1-infected lung epithelial (A549) cells. NAC at concentrations ranging from 5 to 15mM reduced H5N1-induced cytopathogenic effects (CPEs), virus-induced apoptosis and infectious viral yields 24h post-infection. NAC also decreased the production of pro-inflammatory molecules (CXCL8, CXCL10, CCL5 and interleukin-6 (IL-6)) in H5N1-infected A549 cells and reduced monocyte migration towards supernatants of H5N1-infected A549 cells. The antiviral and anti-inflammatory mechanisms of NAC included inhibition of activation of oxidant sensitive pathways including transcription factor NF-κB and mitogen activated protein kinase p38. Pharmacological inhibitors of NF-κB (BAY 11-7085) or p38 (SB203580) exerted similar effects like those determined for NAC in H5N1-infected cells. 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 pro-inflammatory molecules. Therefore, antioxidants like NAC represent a potential additional treatment option that could be considered in the case of an influenza A virus pandemic.</description><identifier>ISSN: 0006-2952</identifier><identifier>EISSN: 1873-2968</identifier><identifier>DOI: 10.1016/j.bcp.2009.08.025</identifier><identifier>PMID: 19732754</identifier><identifier>CODEN: BCPCA6</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>Acetylcysteine - pharmacology ; Acetylcysteine - therapeutic use ; Animals ; Antiviral Agents - pharmacology ; Antiviral Agents - therapeutic use ; Apoptosis ; Biological and medical sciences ; Cell Line, Tumor ; Cells, Cultured ; Cercopithecus aethiops ; Cytokines ; Gene Expression Regulation, Viral - drug effects ; Gene Expression Regulation, Viral - physiology ; H5N1 ; Humans ; Inflammation Mediators - antagonists & inhibitors ; Inflammation Mediators - metabolism ; Influenza A virus ; Influenza A Virus, H5N1 Subtype - drug effects ; Influenza A Virus, H5N1 Subtype - physiology ; Influenza, Human - metabolism ; Influenza, Human - prevention & control ; Medical sciences ; NAC ; Pharmacology. Drug treatments ; ROS ; Vero Cells ; Virus Replication - drug effects ; Virus Replication - physiology</subject><ispartof>Biochemical pharmacology, 2010-02, Vol.79 (3), p.413-420</ispartof><rights>2009 Elsevier Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c539t-3c0dacc2c01c0a7062b575a7953cb7d0bcf2315e5309c2b8bf4e8c418320ed5d3</citedby><cites>FETCH-LOGICAL-c539t-3c0dacc2c01c0a7062b575a7953cb7d0bcf2315e5309c2b8bf4e8c418320ed5d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S000629520900728X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22319230$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19732754$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-00538093$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Geiler, Janina</creatorcontrib><creatorcontrib>Michaelis, Martin</creatorcontrib><creatorcontrib>Naczk, Patrizia</creatorcontrib><creatorcontrib>Leutz, Anke</creatorcontrib><creatorcontrib>Langer, Klaus</creatorcontrib><creatorcontrib>Doerr, Hans-Wilhelm</creatorcontrib><creatorcontrib>Cinatl, Jindrich</creatorcontrib><title>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</title><title>Biochemical pharmacology</title><addtitle>Biochem Pharmacol</addtitle><description>The antioxidant N-acetyl-l-cysteine (NAC) had been shown to inhibit replication of seasonal human influenza A viruses. Here, the effects of NAC on virus replication, virus-induced pro-inflammatory responses and virus-induced apoptosis were investigated in H5N1-infected lung epithelial (A549) cells. NAC at concentrations ranging from 5 to 15mM reduced H5N1-induced cytopathogenic effects (CPEs), virus-induced apoptosis and infectious viral yields 24h post-infection. NAC also decreased the production of pro-inflammatory molecules (CXCL8, CXCL10, CCL5 and interleukin-6 (IL-6)) in H5N1-infected A549 cells and reduced monocyte migration towards supernatants of H5N1-infected A549 cells. The antiviral and anti-inflammatory mechanisms of NAC included inhibition of activation of oxidant sensitive pathways including transcription factor NF-κB and mitogen activated protein kinase p38. Pharmacological inhibitors of NF-κB (BAY 11-7085) or p38 (SB203580) exerted similar effects like those determined for NAC in H5N1-infected cells. 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 pro-inflammatory molecules. Therefore, antioxidants like NAC represent a potential additional treatment option that could be considered in the case of an influenza A virus pandemic.</description><subject>Acetylcysteine - pharmacology</subject><subject>Acetylcysteine - therapeutic use</subject><subject>Animals</subject><subject>Antiviral Agents - pharmacology</subject><subject>Antiviral Agents - therapeutic use</subject><subject>Apoptosis</subject><subject>Biological and medical sciences</subject><subject>Cell Line, Tumor</subject><subject>Cells, Cultured</subject><subject>Cercopithecus aethiops</subject><subject>Cytokines</subject><subject>Gene Expression Regulation, Viral - drug effects</subject><subject>Gene Expression Regulation, Viral - physiology</subject><subject>H5N1</subject><subject>Humans</subject><subject>Inflammation Mediators - antagonists & inhibitors</subject><subject>Inflammation Mediators - metabolism</subject><subject>Influenza A virus</subject><subject>Influenza A Virus, H5N1 Subtype - drug effects</subject><subject>Influenza A Virus, H5N1 Subtype - physiology</subject><subject>Influenza, Human - metabolism</subject><subject>Influenza, Human - prevention & control</subject><subject>Medical sciences</subject><subject>NAC</subject><subject>Pharmacology. Drug treatments</subject><subject>ROS</subject><subject>Vero Cells</subject><subject>Virus Replication - drug effects</subject><subject>Virus Replication - physiology</subject><issn>0006-2952</issn><issn>1873-2968</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc2u0zAQhSME4pYLD8AGeYPgLlLGdpzEYlVVQJGqsoG15TiTG1fOD3ZSKA_Ec-Ko1WUHK_tY3xzPzEmSlxTWFGj-7riuzLhmAHIN5RqYeJSsaFnwlMm8fJysACCPd8FukmchHBdZ5vRpckNlwVkhslXy-5Bqg9PZpS415zCh7ZG8PWy2d8T2ra3sFMjJ-jkQj6OzRk926Inua4I_R48hLHJoyOiH1PaN012np8GfSTc4NLPDEH3IRmSSGHRuUQ2aCWvyw04tae19685k1FM73GNvDdmJA10gN2P_S5PN5ffnyZNGu4Avrudt8u3jh6_bXbr_8unzdrNPjeBySrmBWhvDDFADuoCcVaIQupCCm6qooTIN41Sg4CANq8qqybA0GS05A6xFzW-Tu4tvq50ave20P6tBW7Xb7NXyBiB4CZKfaGTfXNg4-_cZw6Q6G5YhdY_DHFSRiTxjspT_J3lGBQgqIkkvpPFDCB6bhyYoqCVzdVQxc7VkrqBUMfNY8-rqPlcd1n8rriFH4PUV0MFo13jdGxseOBZXIhmHyL2_cBg3fLLoVTAWe4O19TEzVQ_2H238AXbjygc</recordid><startdate>20100201</startdate><enddate>20100201</enddate><creator>Geiler, Janina</creator><creator>Michaelis, Martin</creator><creator>Naczk, Patrizia</creator><creator>Leutz, Anke</creator><creator>Langer, Klaus</creator><creator>Doerr, Hans-Wilhelm</creator><creator>Cinatl, Jindrich</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7T7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>1XC</scope><scope>VOOES</scope></search><sort><creationdate>20100201</creationdate><title>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</title><author>Geiler, Janina ; Michaelis, Martin ; Naczk, Patrizia ; Leutz, Anke ; Langer, Klaus ; Doerr, Hans-Wilhelm ; Cinatl, Jindrich</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c539t-3c0dacc2c01c0a7062b575a7953cb7d0bcf2315e5309c2b8bf4e8c418320ed5d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Acetylcysteine - pharmacology</topic><topic>Acetylcysteine - therapeutic use</topic><topic>Animals</topic><topic>Antiviral Agents - pharmacology</topic><topic>Antiviral Agents - therapeutic use</topic><topic>Apoptosis</topic><topic>Biological and medical sciences</topic><topic>Cell Line, Tumor</topic><topic>Cells, Cultured</topic><topic>Cercopithecus aethiops</topic><topic>Cytokines</topic><topic>Gene Expression Regulation, Viral - drug effects</topic><topic>Gene Expression Regulation, Viral - physiology</topic><topic>H5N1</topic><topic>Humans</topic><topic>Inflammation Mediators - antagonists & inhibitors</topic><topic>Inflammation Mediators - metabolism</topic><topic>Influenza A virus</topic><topic>Influenza A Virus, H5N1 Subtype - drug effects</topic><topic>Influenza A Virus, H5N1 Subtype - physiology</topic><topic>Influenza, Human - metabolism</topic><topic>Influenza, Human - prevention & control</topic><topic>Medical sciences</topic><topic>NAC</topic><topic>Pharmacology. 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Here, the effects of NAC on virus replication, virus-induced pro-inflammatory responses and virus-induced apoptosis were investigated in H5N1-infected lung epithelial (A549) cells. NAC at concentrations ranging from 5 to 15mM reduced H5N1-induced cytopathogenic effects (CPEs), virus-induced apoptosis and infectious viral yields 24h post-infection. NAC also decreased the production of pro-inflammatory molecules (CXCL8, CXCL10, CCL5 and interleukin-6 (IL-6)) in H5N1-infected A549 cells and reduced monocyte migration towards supernatants of H5N1-infected A549 cells. The antiviral and anti-inflammatory mechanisms of NAC included inhibition of activation of oxidant sensitive pathways including transcription factor NF-κB and mitogen activated protein kinase p38. Pharmacological inhibitors of NF-κB (BAY 11-7085) or p38 (SB203580) exerted similar effects like those determined for NAC in H5N1-infected cells. 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 pro-inflammatory molecules. Therefore, antioxidants like NAC represent a potential additional treatment option that could be considered in the case of an influenza A virus pandemic.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>19732754</pmid><doi>10.1016/j.bcp.2009.08.025</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acetylcysteine - pharmacology Acetylcysteine - therapeutic use Animals Antiviral Agents - pharmacology Antiviral Agents - therapeutic use Apoptosis Biological and medical sciences Cell Line, Tumor Cells, Cultured Cercopithecus aethiops Cytokines Gene Expression Regulation, Viral - drug effects Gene Expression Regulation, Viral - physiology H5N1 Humans Inflammation Mediators - antagonists & inhibitors Inflammation Mediators - metabolism Influenza A virus Influenza A Virus, H5N1 Subtype - drug effects Influenza A Virus, H5N1 Subtype - physiology Influenza, Human - metabolism Influenza, Human - prevention & control Medical sciences NAC Pharmacology. Drug treatments ROS Vero Cells Virus Replication - drug effects Virus Replication - physiology |
| title | 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 |
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