Vibrio cholerae porin OmpU induces pro-inflammatory responses, but down-regulates LPS-mediated effects in RAW 264.7, THP-1 and human PBMCs
Vibrio cholerae porin OmpU plays a crucial role in the survival of the organism in the human gut. Various observations suggest critical involvement of OmpU in V. cholerae pathogenesis. However, OmpU is poorly characterized in terms of its ability to evoke cellular responses, particularly in the cont...
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| description | Vibrio cholerae porin OmpU plays a crucial role in the survival of the organism in the human gut. Various observations suggest critical involvement of OmpU in V. cholerae pathogenesis. However, OmpU is poorly characterized in terms of its ability to evoke cellular responses, particularly in the context of host immune system. Therefore, towards characterizing V. cholerae OmpU for its host immunomodulatory functions, we have studied the ability of OmpU to elicit pro-inflammatory responses in a range of immune cells which include, mouse RAW 264.7 macrophages, human THP-1 monocytes and human PBMCs. We have observed that purified OmpU induces pro-inflammatory responses in terms of production of NO, TNFα and IL-6. Interestingly, pre-treatment of the cells with OmpU suppresses the production of NO, TNFα, IL-6 as well as IL-12 upon subsequent activation with LPS. Our results therefore suggest that V. cholerae OmpU may have a differential regulatory role in terms of host immunomodulatory function: it can induce pro-inflammatory responses in target host immune cells, whereas it can also exert suppressive effect on LPS-induced pro-inflammatory responses. In addition, our study indicates that purified OmpU may have the ability to skew the Th1 response towards the Th2 response, presumably via suppression of IL-12 production. |
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Various observations suggest critical involvement of OmpU in V. cholerae pathogenesis. However, OmpU is poorly characterized in terms of its ability to evoke cellular responses, particularly in the context of host immune system. Therefore, towards characterizing V. cholerae OmpU for its host immunomodulatory functions, we have studied the ability of OmpU to elicit pro-inflammatory responses in a range of immune cells which include, mouse RAW 264.7 macrophages, human THP-1 monocytes and human PBMCs. We have observed that purified OmpU induces pro-inflammatory responses in terms of production of NO, TNFα and IL-6. Interestingly, pre-treatment of the cells with OmpU suppresses the production of NO, TNFα, IL-6 as well as IL-12 upon subsequent activation with LPS. Our results therefore suggest that V. cholerae OmpU may have a differential regulatory role in terms of host immunomodulatory function: it can induce pro-inflammatory responses in target host immune cells, whereas it can also exert suppressive effect on LPS-induced pro-inflammatory responses. In addition, our study indicates that purified OmpU may have the ability to skew the Th1 response towards the Th2 response, presumably via suppression of IL-12 production.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0076583</identifier><identifier>PMID: 24086753</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adhesins, Bacterial - pharmacology ; Animals ; Cell Line ; Down-Regulation - drug effects ; Down-Regulation - immunology ; Humans ; Immune system ; Immunomodulation ; Immunomodulation - drug effects ; Inflammation ; Inflammation - immunology ; Inflammation - metabolism ; Interleukin 12 ; Interleukin 6 ; Interleukin-12 - biosynthesis ; Kinases ; Leukocytes, Mononuclear - drug effects ; Leukocytes, Mononuclear - immunology ; Leukocytes, Mononuclear - metabolism ; Lipopolysaccharides ; Lipopolysaccharides - pharmacology ; Lutjanus erythropterus ; Lymphocytes T ; Macrophages ; Mice ; Monocytes ; Nitric Oxide - biosynthesis ; Pathogenesis ; Pathogens ; Pretreatment ; Rodents ; Scophthalmus maximus ; Tumor necrosis factor-TNF ; Tumor necrosis factor-α ; Vibrio alginolyticus ; Vibrio cholerae ; Water-borne diseases ; Waterborne diseases</subject><ispartof>PloS one, 2013-09, Vol.8 (9), p.e76583</ispartof><rights>2013 Sakharwade 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>2013 Sakharwade et al 2013 Sakharwade et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-6e39760845479d86456d3d9419e7e3dd09bc448c59d1e33a6660d499ccd3942f3</citedby><cites>FETCH-LOGICAL-c526t-6e39760845479d86456d3d9419e7e3dd09bc448c59d1e33a6660d499ccd3942f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785423/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785423/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24086753$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sakharwade, Sanica C</creatorcontrib><creatorcontrib>Sharma, Praveen K</creatorcontrib><creatorcontrib>Mukhopadhaya, Arunika</creatorcontrib><title>Vibrio cholerae porin OmpU induces pro-inflammatory responses, but down-regulates LPS-mediated effects in RAW 264.7, THP-1 and human PBMCs</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Vibrio cholerae porin OmpU plays a crucial role in the survival of the organism in the human gut. Various observations suggest critical involvement of OmpU in V. cholerae pathogenesis. However, OmpU is poorly characterized in terms of its ability to evoke cellular responses, particularly in the context of host immune system. Therefore, towards characterizing V. cholerae OmpU for its host immunomodulatory functions, we have studied the ability of OmpU to elicit pro-inflammatory responses in a range of immune cells which include, mouse RAW 264.7 macrophages, human THP-1 monocytes and human PBMCs. We have observed that purified OmpU induces pro-inflammatory responses in terms of production of NO, TNFα and IL-6. Interestingly, pre-treatment of the cells with OmpU suppresses the production of NO, TNFα, IL-6 as well as IL-12 upon subsequent activation with LPS. Our results therefore suggest that V. cholerae OmpU may have a differential regulatory role in terms of host immunomodulatory function: it can induce pro-inflammatory responses in target host immune cells, whereas it can also exert suppressive effect on LPS-induced pro-inflammatory responses. In addition, our study indicates that purified OmpU may have the ability to skew the Th1 response towards the Th2 response, presumably via suppression of IL-12 production.</description><subject>Adhesins, Bacterial - pharmacology</subject><subject>Animals</subject><subject>Cell Line</subject><subject>Down-Regulation - drug effects</subject><subject>Down-Regulation - immunology</subject><subject>Humans</subject><subject>Immune system</subject><subject>Immunomodulation</subject><subject>Immunomodulation - drug effects</subject><subject>Inflammation</subject><subject>Inflammation - immunology</subject><subject>Inflammation - metabolism</subject><subject>Interleukin 12</subject><subject>Interleukin 6</subject><subject>Interleukin-12 - biosynthesis</subject><subject>Kinases</subject><subject>Leukocytes, Mononuclear - drug effects</subject><subject>Leukocytes, Mononuclear - immunology</subject><subject>Leukocytes, Mononuclear - metabolism</subject><subject>Lipopolysaccharides</subject><subject>Lipopolysaccharides - 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Various observations suggest critical involvement of OmpU in V. cholerae pathogenesis. However, OmpU is poorly characterized in terms of its ability to evoke cellular responses, particularly in the context of host immune system. Therefore, towards characterizing V. cholerae OmpU for its host immunomodulatory functions, we have studied the ability of OmpU to elicit pro-inflammatory responses in a range of immune cells which include, mouse RAW 264.7 macrophages, human THP-1 monocytes and human PBMCs. We have observed that purified OmpU induces pro-inflammatory responses in terms of production of NO, TNFα and IL-6. Interestingly, pre-treatment of the cells with OmpU suppresses the production of NO, TNFα, IL-6 as well as IL-12 upon subsequent activation with LPS. Our results therefore suggest that V. cholerae OmpU may have a differential regulatory role in terms of host immunomodulatory function: it can induce pro-inflammatory responses in target host immune cells, whereas it can also exert suppressive effect on LPS-induced pro-inflammatory responses. In addition, our study indicates that purified OmpU may have the ability to skew the Th1 response towards the Th2 response, presumably via suppression of IL-12 production.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24086753</pmid><doi>10.1371/journal.pone.0076583</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Adhesins, Bacterial - pharmacology Animals Cell Line Down-Regulation - drug effects Down-Regulation - immunology Humans Immune system Immunomodulation Immunomodulation - drug effects Inflammation Inflammation - immunology Inflammation - metabolism Interleukin 12 Interleukin 6 Interleukin-12 - biosynthesis Kinases Leukocytes, Mononuclear - drug effects Leukocytes, Mononuclear - immunology Leukocytes, Mononuclear - metabolism Lipopolysaccharides Lipopolysaccharides - pharmacology Lutjanus erythropterus Lymphocytes T Macrophages Mice Monocytes Nitric Oxide - biosynthesis Pathogenesis Pathogens Pretreatment Rodents Scophthalmus maximus Tumor necrosis factor-TNF Tumor necrosis factor-α Vibrio alginolyticus Vibrio cholerae Water-borne diseases Waterborne diseases |
| title | Vibrio cholerae porin OmpU induces pro-inflammatory responses, but down-regulates LPS-mediated effects in RAW 264.7, THP-1 and human PBMCs |
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