Photo-oxidation products of skin surface squalene mediate metabolic and inflammatory responses to solar UV in human keratinocytes
The study aimed to identify endogenous lipid mediators of metabolic and inflammatory responses of human keratinocytes to solar UV irradiation. Physiologically relevant doses of solar simulated UVA+UVB were applied to human skin surface lipids (SSL) or to primary cultures of normal human epidermal ke...
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description | The study aimed to identify endogenous lipid mediators of metabolic and inflammatory responses of human keratinocytes to solar UV irradiation. Physiologically relevant doses of solar simulated UVA+UVB were applied to human skin surface lipids (SSL) or to primary cultures of normal human epidermal keratinocytes (NHEK). The decay of photo-sensitive lipid-soluble components, alpha-tocopherol, squalene (Sq), and cholesterol in SSL was analysed and products of squalene photo-oxidation (SqPx) were quantitatively isolated from irradiated SSL. When administered directly to NHEK, low-dose solar UVA+UVB induced time-dependent inflammatory and metabolic responses. To mimic UVA+UVB action, NHEK were exposed to intact or photo-oxidised SSL, Sq or SqPx, 4-hydroxy-2-nonenal (4-HNE), and the product of tryptophan photo-oxidation 6-formylindolo[3,2-b]carbazole (FICZ). FICZ activated exclusively metabolic responses characteristic for UV, i.e. the aryl hydrocarbon receptor (AhR) machinery and downstream CYP1A1/CYP1B1 gene expression, while 4-HNE slightly stimulated inflammatory UV markers IL-6, COX-2, and iNOS genes. On contrast, SqPx induced the majority of metabolic and inflammatory responses characteristic for UVA+UVB, acting via AhR, EGFR, and G-protein-coupled arachidonic acid receptor (G2A).
Our findings indicate that Sq could be a primary sensor of solar UV irradiation in human SSL, and products of its photo-oxidation mediate/induce metabolic and inflammatory responses of keratinocytes to UVA+UVB, which could be relevant for skin inflammation in the sun-exposed oily skin. |
doi_str_mv | 10.1371/journal.pone.0044472 |
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Our findings indicate that Sq could be a primary sensor of solar UV irradiation in human SSL, and products of its photo-oxidation mediate/induce metabolic and inflammatory responses of keratinocytes to UVA+UVB, which could be relevant for skin inflammation in the sun-exposed oily skin.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0044472</identifier><identifier>PMID: 22952984</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Aldehydes - pharmacology ; Arachidonic acid ; Aromatic compounds ; Aryl Hydrocarbon Hydroxylases - metabolism ; Biology ; Carbazole ; Carbazoles - pharmacology ; Causes of ; Cholesterol ; Cyclooxygenase 2 - metabolism ; Cyclooxygenase-2 ; CYP1B1 gene ; Cytochrome P-450 CYP1A1 - metabolism ; Cytochrome P-450 CYP1B1 ; Cytochrome P450 ; Cytokines - genetics ; Cytokines - metabolism ; Dose-Response Relationship, Radiation ; Epidermal growth factor receptors ; Epidermis - pathology ; ErbB Receptors - metabolism ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Gene expression ; Gene Expression Regulation - drug effects ; Gene Expression Regulation - radiation effects ; Genetic aspects ; Human behavior ; Humans ; Inflammation ; Inflammation - pathology ; Interleukin 6 ; Irradiation ; Isoenzymes - metabolism ; Keratinocytes ; Keratinocytes - enzymology ; Keratinocytes - metabolism ; Keratinocytes - pathology ; Keratinocytes - radiation effects ; Kinases ; Lipids ; Machinery ; Machinery and equipment ; Male ; Nitric Oxide Synthase Type II - metabolism ; Nitric-oxide synthase ; Oxidation ; Oxidation-Reduction - drug effects ; Oxidation-Reduction - radiation effects ; Photooxidation ; Physics ; Physiological aspects ; Receptors, Aryl Hydrocarbon - metabolism ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Signal Transduction - drug effects ; Signal Transduction - radiation effects ; Skin ; Skin - radiation effects ; Squalene ; Squalene - pharmacology ; Surface Properties - drug effects ; Surface Properties - radiation effects ; Time Factors ; Tocopherol ; Tryptophan ; U.V. radiation ; Ultraviolet radiation ; Ultraviolet Rays</subject><ispartof>PloS one, 2012-08, Vol.7 (8), p.e44472</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>Kostyuk et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2012 Kostyuk et al 2012 Kostyuk et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-b1ac22e0d21bc59781fc13409f5da536271d8025d577984ae98e5e5c716bc32b3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3431355/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3431355/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22952984$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Tsuji, Yoshiaki</contributor><creatorcontrib>Kostyuk, Vladimir</creatorcontrib><creatorcontrib>Potapovich, Alla</creatorcontrib><creatorcontrib>Stancato, Andrea</creatorcontrib><creatorcontrib>De Luca, Chiara</creatorcontrib><creatorcontrib>Lulli, Daniela</creatorcontrib><creatorcontrib>Pastore, Saveria</creatorcontrib><creatorcontrib>Korkina, Liudmila</creatorcontrib><title>Photo-oxidation products of skin surface squalene mediate metabolic and inflammatory responses to solar UV in human keratinocytes</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The study aimed to identify endogenous lipid mediators of metabolic and inflammatory responses of human keratinocytes to solar UV irradiation. Physiologically relevant doses of solar simulated UVA+UVB were applied to human skin surface lipids (SSL) or to primary cultures of normal human epidermal keratinocytes (NHEK). The decay of photo-sensitive lipid-soluble components, alpha-tocopherol, squalene (Sq), and cholesterol in SSL was analysed and products of squalene photo-oxidation (SqPx) were quantitatively isolated from irradiated SSL. When administered directly to NHEK, low-dose solar UVA+UVB induced time-dependent inflammatory and metabolic responses. To mimic UVA+UVB action, NHEK were exposed to intact or photo-oxidised SSL, Sq or SqPx, 4-hydroxy-2-nonenal (4-HNE), and the product of tryptophan photo-oxidation 6-formylindolo[3,2-b]carbazole (FICZ). FICZ activated exclusively metabolic responses characteristic for UV, i.e. the aryl hydrocarbon receptor (AhR) machinery and downstream CYP1A1/CYP1B1 gene expression, while 4-HNE slightly stimulated inflammatory UV markers IL-6, COX-2, and iNOS genes. On contrast, SqPx induced the majority of metabolic and inflammatory responses characteristic for UVA+UVB, acting via AhR, EGFR, and G-protein-coupled arachidonic acid receptor (G2A).
Our findings indicate that Sq could be a primary sensor of solar UV irradiation in human SSL, and products of its photo-oxidation mediate/induce metabolic and inflammatory responses of keratinocytes to UVA+UVB, which could be relevant for skin inflammation in the sun-exposed oily skin.</description><subject>Adult</subject><subject>Aldehydes - pharmacology</subject><subject>Arachidonic acid</subject><subject>Aromatic compounds</subject><subject>Aryl Hydrocarbon Hydroxylases - metabolism</subject><subject>Biology</subject><subject>Carbazole</subject><subject>Carbazoles - pharmacology</subject><subject>Causes of</subject><subject>Cholesterol</subject><subject>Cyclooxygenase 2 - metabolism</subject><subject>Cyclooxygenase-2</subject><subject>CYP1B1 gene</subject><subject>Cytochrome P-450 CYP1A1 - metabolism</subject><subject>Cytochrome P-450 CYP1B1</subject><subject>Cytochrome P450</subject><subject>Cytokines - genetics</subject><subject>Cytokines - metabolism</subject><subject>Dose-Response Relationship, Radiation</subject><subject>Epidermal growth factor receptors</subject><subject>Epidermis - pathology</subject><subject>ErbB Receptors - metabolism</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>Gene expression</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Gene Expression Regulation - radiation effects</subject><subject>Genetic aspects</subject><subject>Human behavior</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Inflammation - pathology</subject><subject>Interleukin 6</subject><subject>Irradiation</subject><subject>Isoenzymes - metabolism</subject><subject>Keratinocytes</subject><subject>Keratinocytes - enzymology</subject><subject>Keratinocytes - metabolism</subject><subject>Keratinocytes - pathology</subject><subject>Keratinocytes - radiation effects</subject><subject>Kinases</subject><subject>Lipids</subject><subject>Machinery</subject><subject>Machinery and equipment</subject><subject>Male</subject><subject>Nitric Oxide Synthase Type II - metabolism</subject><subject>Nitric-oxide synthase</subject><subject>Oxidation</subject><subject>Oxidation-Reduction - 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pharmacology</topic><topic>Arachidonic acid</topic><topic>Aromatic compounds</topic><topic>Aryl Hydrocarbon Hydroxylases - metabolism</topic><topic>Biology</topic><topic>Carbazole</topic><topic>Carbazoles - pharmacology</topic><topic>Causes of</topic><topic>Cholesterol</topic><topic>Cyclooxygenase 2 - metabolism</topic><topic>Cyclooxygenase-2</topic><topic>CYP1B1 gene</topic><topic>Cytochrome P-450 CYP1A1 - metabolism</topic><topic>Cytochrome P-450 CYP1B1</topic><topic>Cytochrome P450</topic><topic>Cytokines - genetics</topic><topic>Cytokines - metabolism</topic><topic>Dose-Response Relationship, Radiation</topic><topic>Epidermal growth factor receptors</topic><topic>Epidermis - pathology</topic><topic>ErbB Receptors - metabolism</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>Gene expression</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Gene Expression Regulation - radiation effects</topic><topic>Genetic aspects</topic><topic>Human behavior</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Inflammation - pathology</topic><topic>Interleukin 6</topic><topic>Irradiation</topic><topic>Isoenzymes - metabolism</topic><topic>Keratinocytes</topic><topic>Keratinocytes - enzymology</topic><topic>Keratinocytes - metabolism</topic><topic>Keratinocytes - pathology</topic><topic>Keratinocytes - radiation effects</topic><topic>Kinases</topic><topic>Lipids</topic><topic>Machinery</topic><topic>Machinery and equipment</topic><topic>Male</topic><topic>Nitric Oxide Synthase Type II - metabolism</topic><topic>Nitric-oxide synthase</topic><topic>Oxidation</topic><topic>Oxidation-Reduction - drug effects</topic><topic>Oxidation-Reduction - radiation effects</topic><topic>Photooxidation</topic><topic>Physics</topic><topic>Physiological aspects</topic><topic>Receptors, Aryl Hydrocarbon - metabolism</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Signal Transduction - drug effects</topic><topic>Signal Transduction - radiation effects</topic><topic>Skin</topic><topic>Skin - 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Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kostyuk, Vladimir</au><au>Potapovich, Alla</au><au>Stancato, Andrea</au><au>De Luca, Chiara</au><au>Lulli, Daniela</au><au>Pastore, Saveria</au><au>Korkina, Liudmila</au><au>Tsuji, Yoshiaki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Photo-oxidation products of skin surface squalene mediate metabolic and inflammatory responses to solar UV in human keratinocytes</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-08-30</date><risdate>2012</risdate><volume>7</volume><issue>8</issue><spage>e44472</spage><pages>e44472-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The study aimed to identify endogenous lipid mediators of metabolic and inflammatory responses of human keratinocytes to solar UV irradiation. Physiologically relevant doses of solar simulated UVA+UVB were applied to human skin surface lipids (SSL) or to primary cultures of normal human epidermal keratinocytes (NHEK). The decay of photo-sensitive lipid-soluble components, alpha-tocopherol, squalene (Sq), and cholesterol in SSL was analysed and products of squalene photo-oxidation (SqPx) were quantitatively isolated from irradiated SSL. When administered directly to NHEK, low-dose solar UVA+UVB induced time-dependent inflammatory and metabolic responses. To mimic UVA+UVB action, NHEK were exposed to intact or photo-oxidised SSL, Sq or SqPx, 4-hydroxy-2-nonenal (4-HNE), and the product of tryptophan photo-oxidation 6-formylindolo[3,2-b]carbazole (FICZ). FICZ activated exclusively metabolic responses characteristic for UV, i.e. the aryl hydrocarbon receptor (AhR) machinery and downstream CYP1A1/CYP1B1 gene expression, while 4-HNE slightly stimulated inflammatory UV markers IL-6, COX-2, and iNOS genes. On contrast, SqPx induced the majority of metabolic and inflammatory responses characteristic for UVA+UVB, acting via AhR, EGFR, and G-protein-coupled arachidonic acid receptor (G2A).
Our findings indicate that Sq could be a primary sensor of solar UV irradiation in human SSL, and products of its photo-oxidation mediate/induce metabolic and inflammatory responses of keratinocytes to UVA+UVB, which could be relevant for skin inflammation in the sun-exposed oily skin.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22952984</pmid><doi>10.1371/journal.pone.0044472</doi><tpages>e44472</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2012-08, Vol.7 (8), p.e44472 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_1326512647 |
source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
subjects | Adult Aldehydes - pharmacology Arachidonic acid Aromatic compounds Aryl Hydrocarbon Hydroxylases - metabolism Biology Carbazole Carbazoles - pharmacology Causes of Cholesterol Cyclooxygenase 2 - metabolism Cyclooxygenase-2 CYP1B1 gene Cytochrome P-450 CYP1A1 - metabolism Cytochrome P-450 CYP1B1 Cytochrome P450 Cytokines - genetics Cytokines - metabolism Dose-Response Relationship, Radiation Epidermal growth factor receptors Epidermis - pathology ErbB Receptors - metabolism Extracellular Signal-Regulated MAP Kinases - metabolism Gene expression Gene Expression Regulation - drug effects Gene Expression Regulation - radiation effects Genetic aspects Human behavior Humans Inflammation Inflammation - pathology Interleukin 6 Irradiation Isoenzymes - metabolism Keratinocytes Keratinocytes - enzymology Keratinocytes - metabolism Keratinocytes - pathology Keratinocytes - radiation effects Kinases Lipids Machinery Machinery and equipment Male Nitric Oxide Synthase Type II - metabolism Nitric-oxide synthase Oxidation Oxidation-Reduction - drug effects Oxidation-Reduction - radiation effects Photooxidation Physics Physiological aspects Receptors, Aryl Hydrocarbon - metabolism RNA, Messenger - genetics RNA, Messenger - metabolism Signal Transduction - drug effects Signal Transduction - radiation effects Skin Skin - radiation effects Squalene Squalene - pharmacology Surface Properties - drug effects Surface Properties - radiation effects Time Factors Tocopherol Tryptophan U.V. radiation Ultraviolet radiation Ultraviolet Rays |
title | Photo-oxidation products of skin surface squalene mediate metabolic and inflammatory responses to solar UV in human keratinocytes |
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