Long-term culture with lipopolysaccharide induces dose-dependent cytostatic and cytotoxic effects in THP-1 monocytes
Monocytes act as a first line of defence against invading pathogens and their dysfunctions seem to be a key factor in many immune disorders. However, the data on mechanisms underlying these dysfunctions remain elusive. In this study, we evaluated the effects of long-term (168h) lipopolysaccharide ex...
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description | Monocytes act as a first line of defence against invading pathogens and their dysfunctions seem to be a key factor in many immune disorders. However, the data on mechanisms underlying these dysfunctions remain elusive. In this study, we evaluated the effects of long-term (168h) lipopolysaccharide exposure on monocytes at low density cultures (1×105cells/ml). Treatment with low dose LPS (≤5μg/ml) resulted in oxidative stress induction followed by p21 pathway activation, permanent cell cycle arrest and SASP development. Furthermore, high dose LPS (≥10μg/ml) induced cell death involving mitochondrial pathways, death receptors as well as p21-dependent DNA damage response activation mediated by ROS generation and TNF-α release. Additionally, exposure to high dose of LPS resulted in THP-1 monocytes differentiation to macrophages. In conclusion, long-term culture with LPS exerts in low density monocytes cytostatic/cytotoxic effects in a dose-dependent manner by inducing senescence associated with chronic inflammation at low doses and initiation of cell death at higher doses. These findings shed new light on understanding of monocytes dysfunction, an issue relevant to chronic inflammation and many immune disorders.
[Display omitted]
•Monocyte dysfunctions are a key factor in many immune disorders.•LPS affects monocytes at low density cultures in a dose-dependent manner.•Low-dose LPS induces oxidative stress and permanent cell cycle arrest.•High-dose LPS induces apoptosis mediated by ROS generation and TNF-α release.•High-dose LPS induces THP-1 differentiation to macrophages. |
doi_str_mv | 10.1016/j.tiv.2017.03.009 |
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[Display omitted]
•Monocyte dysfunctions are a key factor in many immune disorders.•LPS affects monocytes at low density cultures in a dose-dependent manner.•Low-dose LPS induces oxidative stress and permanent cell cycle arrest.•High-dose LPS induces apoptosis mediated by ROS generation and TNF-α release.•High-dose LPS induces THP-1 differentiation to macrophages.</description><identifier>ISSN: 0887-2333</identifier><identifier>EISSN: 1879-3177</identifier><identifier>DOI: 10.1016/j.tiv.2017.03.009</identifier><identifier>PMID: 28341289</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Apoptosis ; Calcium - metabolism ; Cell activation ; Cell culture ; Cell cycle ; Cell Cycle Checkpoints - drug effects ; Cell death ; Cell Death - drug effects ; Cell Differentiation - drug effects ; Cell Line, Tumor ; Cell Survival - drug effects ; Cyclin-dependent kinase inhibitor p21 ; Cytotoxicity ; Death receptors ; Density ; Deoxyribonucleic acid ; Disorders ; DNA ; DNA damage ; DNA Fragmentation ; Erythrocytes ; Exposure ; Genotoxicity ; Humans ; Inflammation ; Lipopolysaccharides ; Lipopolysaccharides - pharmacology ; LPS ; Macrophages ; Mitochondria ; Mitochondrial DNA ; Monocytes ; Monocytes - drug effects ; Monocytes - metabolism ; Monocytes - physiology ; Mortality ; Oxidative stress ; Oxidative Stress - drug effects ; Phagocytosis - drug effects ; Premature senescence ; Reactive oxygen species ; Reactive Oxygen Species - metabolism ; Receptors ; Senescence ; Tumor Necrosis Factor-alpha - metabolism ; Tumor necrosis factor-α ; Zinc - metabolism</subject><ispartof>Toxicology in vitro, 2017-08, Vol.42, p.1-9</ispartof><rights>2017 Elsevier Ltd</rights><rights>Copyright © 2017 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Science Ltd. Aug 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c381t-b8f43100f8d0cfa4e616ec67e90f9561ccad67e2dc91e427467f80f419e794583</citedby><cites>FETCH-LOGICAL-c381t-b8f43100f8d0cfa4e616ec67e90f9561ccad67e2dc91e427467f80f419e794583</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.tiv.2017.03.009$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28341289$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mytych, Jennifer</creatorcontrib><creatorcontrib>Romerowicz-Misielak, Maria</creatorcontrib><creatorcontrib>Koziorowski, Marek</creatorcontrib><title>Long-term culture with lipopolysaccharide induces dose-dependent cytostatic and cytotoxic effects in THP-1 monocytes</title><title>Toxicology in vitro</title><addtitle>Toxicol In Vitro</addtitle><description>Monocytes act as a first line of defence against invading pathogens and their dysfunctions seem to be a key factor in many immune disorders. However, the data on mechanisms underlying these dysfunctions remain elusive. In this study, we evaluated the effects of long-term (168h) lipopolysaccharide exposure on monocytes at low density cultures (1×105cells/ml). Treatment with low dose LPS (≤5μg/ml) resulted in oxidative stress induction followed by p21 pathway activation, permanent cell cycle arrest and SASP development. Furthermore, high dose LPS (≥10μg/ml) induced cell death involving mitochondrial pathways, death receptors as well as p21-dependent DNA damage response activation mediated by ROS generation and TNF-α release. Additionally, exposure to high dose of LPS resulted in THP-1 monocytes differentiation to macrophages. In conclusion, long-term culture with LPS exerts in low density monocytes cytostatic/cytotoxic effects in a dose-dependent manner by inducing senescence associated with chronic inflammation at low doses and initiation of cell death at higher doses. These findings shed new light on understanding of monocytes dysfunction, an issue relevant to chronic inflammation and many immune disorders.
[Display omitted]
•Monocyte dysfunctions are a key factor in many immune disorders.•LPS affects monocytes at low density cultures in a dose-dependent manner.•Low-dose LPS induces oxidative stress and permanent cell cycle arrest.•High-dose LPS induces apoptosis mediated by ROS generation and TNF-α release.•High-dose LPS induces THP-1 differentiation to macrophages.</description><subject>Apoptosis</subject><subject>Calcium - metabolism</subject><subject>Cell activation</subject><subject>Cell culture</subject><subject>Cell cycle</subject><subject>Cell Cycle Checkpoints - drug effects</subject><subject>Cell death</subject><subject>Cell Death - drug effects</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>Cyclin-dependent kinase inhibitor p21</subject><subject>Cytotoxicity</subject><subject>Death receptors</subject><subject>Density</subject><subject>Deoxyribonucleic acid</subject><subject>Disorders</subject><subject>DNA</subject><subject>DNA damage</subject><subject>DNA Fragmentation</subject><subject>Erythrocytes</subject><subject>Exposure</subject><subject>Genotoxicity</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Lipopolysaccharides</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>LPS</subject><subject>Macrophages</subject><subject>Mitochondria</subject><subject>Mitochondrial DNA</subject><subject>Monocytes</subject><subject>Monocytes - drug effects</subject><subject>Monocytes - metabolism</subject><subject>Monocytes - physiology</subject><subject>Mortality</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Phagocytosis - drug effects</subject><subject>Premature senescence</subject><subject>Reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Receptors</subject><subject>Senescence</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><subject>Tumor necrosis factor-α</subject><subject>Zinc - metabolism</subject><issn>0887-2333</issn><issn>1879-3177</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEFPGzEQha2KqgmBH9ALssR5t-P1Zm2rJ4RoUykSHNKztdjj4ihZL7Y3NP--pqEcexo9zXtvNB8hnxnUDFj3ZVtnf6gbYKIGXgOoD2TOpFAVZ0KckTlIKaqGcz4j5yltAWApG_hEZo3kLWukmpO8DsOvKmPcUzPt8hSRvvj8RHd-DGPYHVNvzFMfvUXqBzsZTNSGhJXFEQeLQ6bmmEPKffaG9oP9K3P4XRQ6hyankqOb1UPF6D4MoawxXZCPrt8lvHybC_Lz293mdlWt77__uL1ZV4ZLlqtH6VrOAJy0YFzfYsc6NJ1ABU4tO2ZMb4tqrFEM20a0nXASXMsUCtUuJV-Q61PvGMPzhCnrbZjiUE7qBiSXoCSI4mInl4khpYhOj9Hv-3jUDPQrZ73VhbN-5ayB68K5ZK7emqfHPdr3xD-wxfD1ZMDy38Fj1Ml4HAxaHwsVbYP_T_0fjl-PvQ</recordid><startdate>201708</startdate><enddate>201708</enddate><creator>Mytych, Jennifer</creator><creator>Romerowicz-Misielak, Maria</creator><creator>Koziorowski, Marek</creator><general>Elsevier Ltd</general><general>Elsevier Science Ltd</general><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>7TK</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>201708</creationdate><title>Long-term culture with lipopolysaccharide induces dose-dependent cytostatic and cytotoxic effects in THP-1 monocytes</title><author>Mytych, Jennifer ; Romerowicz-Misielak, Maria ; Koziorowski, Marek</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c381t-b8f43100f8d0cfa4e616ec67e90f9561ccad67e2dc91e427467f80f419e794583</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Apoptosis</topic><topic>Calcium - metabolism</topic><topic>Cell activation</topic><topic>Cell culture</topic><topic>Cell cycle</topic><topic>Cell Cycle Checkpoints - drug effects</topic><topic>Cell death</topic><topic>Cell Death - drug effects</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival - drug effects</topic><topic>Cyclin-dependent kinase inhibitor p21</topic><topic>Cytotoxicity</topic><topic>Death receptors</topic><topic>Density</topic><topic>Deoxyribonucleic acid</topic><topic>Disorders</topic><topic>DNA</topic><topic>DNA damage</topic><topic>DNA Fragmentation</topic><topic>Erythrocytes</topic><topic>Exposure</topic><topic>Genotoxicity</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Lipopolysaccharides</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>LPS</topic><topic>Macrophages</topic><topic>Mitochondria</topic><topic>Mitochondrial DNA</topic><topic>Monocytes</topic><topic>Monocytes - drug effects</topic><topic>Monocytes - metabolism</topic><topic>Monocytes - physiology</topic><topic>Mortality</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Phagocytosis - drug effects</topic><topic>Premature senescence</topic><topic>Reactive oxygen species</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Receptors</topic><topic>Senescence</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><topic>Tumor necrosis factor-α</topic><topic>Zinc - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mytych, Jennifer</creatorcontrib><creatorcontrib>Romerowicz-Misielak, Maria</creatorcontrib><creatorcontrib>Koziorowski, Marek</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Toxicology in vitro</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mytych, Jennifer</au><au>Romerowicz-Misielak, Maria</au><au>Koziorowski, Marek</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Long-term culture with lipopolysaccharide induces dose-dependent cytostatic and cytotoxic effects in THP-1 monocytes</atitle><jtitle>Toxicology in vitro</jtitle><addtitle>Toxicol In Vitro</addtitle><date>2017-08</date><risdate>2017</risdate><volume>42</volume><spage>1</spage><epage>9</epage><pages>1-9</pages><issn>0887-2333</issn><eissn>1879-3177</eissn><abstract>Monocytes act as a first line of defence against invading pathogens and their dysfunctions seem to be a key factor in many immune disorders. However, the data on mechanisms underlying these dysfunctions remain elusive. In this study, we evaluated the effects of long-term (168h) lipopolysaccharide exposure on monocytes at low density cultures (1×105cells/ml). Treatment with low dose LPS (≤5μg/ml) resulted in oxidative stress induction followed by p21 pathway activation, permanent cell cycle arrest and SASP development. Furthermore, high dose LPS (≥10μg/ml) induced cell death involving mitochondrial pathways, death receptors as well as p21-dependent DNA damage response activation mediated by ROS generation and TNF-α release. Additionally, exposure to high dose of LPS resulted in THP-1 monocytes differentiation to macrophages. In conclusion, long-term culture with LPS exerts in low density monocytes cytostatic/cytotoxic effects in a dose-dependent manner by inducing senescence associated with chronic inflammation at low doses and initiation of cell death at higher doses. These findings shed new light on understanding of monocytes dysfunction, an issue relevant to chronic inflammation and many immune disorders.
[Display omitted]
•Monocyte dysfunctions are a key factor in many immune disorders.•LPS affects monocytes at low density cultures in a dose-dependent manner.•Low-dose LPS induces oxidative stress and permanent cell cycle arrest.•High-dose LPS induces apoptosis mediated by ROS generation and TNF-α release.•High-dose LPS induces THP-1 differentiation to macrophages.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>28341289</pmid><doi>10.1016/j.tiv.2017.03.009</doi><tpages>9</tpages></addata></record> |
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subjects | Apoptosis Calcium - metabolism Cell activation Cell culture Cell cycle Cell Cycle Checkpoints - drug effects Cell death Cell Death - drug effects Cell Differentiation - drug effects Cell Line, Tumor Cell Survival - drug effects Cyclin-dependent kinase inhibitor p21 Cytotoxicity Death receptors Density Deoxyribonucleic acid Disorders DNA DNA damage DNA Fragmentation Erythrocytes Exposure Genotoxicity Humans Inflammation Lipopolysaccharides Lipopolysaccharides - pharmacology LPS Macrophages Mitochondria Mitochondrial DNA Monocytes Monocytes - drug effects Monocytes - metabolism Monocytes - physiology Mortality Oxidative stress Oxidative Stress - drug effects Phagocytosis - drug effects Premature senescence Reactive oxygen species Reactive Oxygen Species - metabolism Receptors Senescence Tumor Necrosis Factor-alpha - metabolism Tumor necrosis factor-α Zinc - metabolism |
title | Long-term culture with lipopolysaccharide induces dose-dependent cytostatic and cytotoxic effects in THP-1 monocytes |
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