Lipopolysaccharide stimulates adrenal steroidogenesis in rodent cells by a NFκB-dependent mechanism involving COX-2 activation
Stimulation of adrenal steroidogenesis is involved in the HPA response to exogenous noxa. Although inflammatory cytokines can mediate the LPS-triggered activation of the HPA, direct effects of LPS on glucocorticoid release have been described. Present studies were undertaken to characterize the mole...
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| Veröffentlicht in: | Molecular and cellular endocrinology 2011-04, Vol.337 (1), p.1-6 |
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| creator | Martinez Calejman, C. Astort, F. Di Gruccio, J.M. Repetto, E.M. Mercau, M. Giordanino, E. Sanchez, R. Pignataro, O. Arias, P. Cymeryng, C.B. |
| description | Stimulation of adrenal steroidogenesis is involved in the HPA response to exogenous noxa. Although inflammatory cytokines can mediate the LPS-triggered activation of the HPA, direct effects of LPS on glucocorticoid release have been described. Present studies were undertaken to characterize the molecular mechanisms underlying the effect of LPS on steroid secretion in isolated rodent adrenal cells, assessing the participation of NFκB and COX-2 activities in this response.
Our results show that LPS treatment stimulates steroidogenesis in murine and rat adrenocortical cells, and that Y1 cells express the binding-transducing complex TLR-4/CD14/MD-2, as demonstrated by RT-PCR. NFκB activity and COX-2 protein levels are increased in this cell line by LPS treatment, and pharmacologic and molecular manipulation of the NFκB pathway significantly affected both COX-2 protein levels and steroid production. Finally, pharmacological inhibition of COX-2 activity significantly impairs steroid production. Thus, our results strongly suggest that the mechanism involved in the stimulation of steroidogenesis by LPS in rodent adrenal cells involves the activation of the NFκB signaling pathway and the induction of COX-2. |
| doi_str_mv | 10.1016/j.mce.2010.12.036 |
| format | Article |
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Our results show that LPS treatment stimulates steroidogenesis in murine and rat adrenocortical cells, and that Y1 cells express the binding-transducing complex TLR-4/CD14/MD-2, as demonstrated by RT-PCR. NFκB activity and COX-2 protein levels are increased in this cell line by LPS treatment, and pharmacologic and molecular manipulation of the NFκB pathway significantly affected both COX-2 protein levels and steroid production. Finally, pharmacological inhibition of COX-2 activity significantly impairs steroid production. Thus, our results strongly suggest that the mechanism involved in the stimulation of steroidogenesis by LPS in rodent adrenal cells involves the activation of the NFκB signaling pathway and the induction of COX-2.</description><identifier>ISSN: 0303-7207</identifier><identifier>EISSN: 1872-8057</identifier><identifier>DOI: 10.1016/j.mce.2010.12.036</identifier><identifier>PMID: 21300135</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>Adrenal cortex ; Adrenal Glands - cytology ; Adrenal Glands - enzymology ; Adrenal Glands - metabolism ; Animals ; Cell Culture Techniques ; Cell Line, Tumor ; Corticosterone - biosynthesis ; Cyclooxygenase 2 - metabolism ; Cyclooxygenase-2 ; cytokines ; Enzyme Activation - drug effects ; Heterocyclic Compounds, 3-Ring - pharmacology ; I-kappa B Kinase - antagonists & inhibitors ; Lipopolysaccharide ; Lipopolysaccharide Receptors - genetics ; Lipopolysaccharide Receptors - metabolism ; lipopolysaccharides ; Lipopolysaccharides - pharmacology ; Lymphocyte Antigen 96 - genetics ; Lymphocyte Antigen 96 - metabolism ; Mice ; NF-kappa B - metabolism ; NFκB ; Phosphoproteins - metabolism ; Progesterone - biosynthesis ; Pyridines - pharmacology ; Rats ; reverse transcriptase polymerase chain reaction ; secretion ; signal transduction ; Signal Transduction - drug effects ; Steroidogenesis ; TLR-4 ; Toll-Like Receptor 4 - genetics ; Toll-Like Receptor 4 - metabolism ; transcription factor NF-kappa B ; Transcription, Genetic - drug effects ; Y1 cells</subject><ispartof>Molecular and cellular endocrinology, 2011-04, Vol.337 (1), p.1-6</ispartof><rights>2011 Elsevier Ireland Ltd</rights><rights>Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c376t-2b7703b355958cab74a6cfdcd2a0b34d714cefe77e9f7eeffb35886c0a75a4363</citedby><cites>FETCH-LOGICAL-c376t-2b7703b355958cab74a6cfdcd2a0b34d714cefe77e9f7eeffb35886c0a75a4363</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0303720711000827$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21300135$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Martinez Calejman, C.</creatorcontrib><creatorcontrib>Astort, F.</creatorcontrib><creatorcontrib>Di Gruccio, J.M.</creatorcontrib><creatorcontrib>Repetto, E.M.</creatorcontrib><creatorcontrib>Mercau, M.</creatorcontrib><creatorcontrib>Giordanino, E.</creatorcontrib><creatorcontrib>Sanchez, R.</creatorcontrib><creatorcontrib>Pignataro, O.</creatorcontrib><creatorcontrib>Arias, P.</creatorcontrib><creatorcontrib>Cymeryng, C.B.</creatorcontrib><title>Lipopolysaccharide stimulates adrenal steroidogenesis in rodent cells by a NFκB-dependent mechanism involving COX-2 activation</title><title>Molecular and cellular endocrinology</title><addtitle>Mol Cell Endocrinol</addtitle><description>Stimulation of adrenal steroidogenesis is involved in the HPA response to exogenous noxa. Although inflammatory cytokines can mediate the LPS-triggered activation of the HPA, direct effects of LPS on glucocorticoid release have been described. Present studies were undertaken to characterize the molecular mechanisms underlying the effect of LPS on steroid secretion in isolated rodent adrenal cells, assessing the participation of NFκB and COX-2 activities in this response.
Our results show that LPS treatment stimulates steroidogenesis in murine and rat adrenocortical cells, and that Y1 cells express the binding-transducing complex TLR-4/CD14/MD-2, as demonstrated by RT-PCR. NFκB activity and COX-2 protein levels are increased in this cell line by LPS treatment, and pharmacologic and molecular manipulation of the NFκB pathway significantly affected both COX-2 protein levels and steroid production. Finally, pharmacological inhibition of COX-2 activity significantly impairs steroid production. Thus, our results strongly suggest that the mechanism involved in the stimulation of steroidogenesis by LPS in rodent adrenal cells involves the activation of the NFκB signaling pathway and the induction of COX-2.</description><subject>Adrenal cortex</subject><subject>Adrenal Glands - cytology</subject><subject>Adrenal Glands - enzymology</subject><subject>Adrenal Glands - metabolism</subject><subject>Animals</subject><subject>Cell Culture Techniques</subject><subject>Cell Line, Tumor</subject><subject>Corticosterone - biosynthesis</subject><subject>Cyclooxygenase 2 - metabolism</subject><subject>Cyclooxygenase-2</subject><subject>cytokines</subject><subject>Enzyme Activation - drug effects</subject><subject>Heterocyclic Compounds, 3-Ring - pharmacology</subject><subject>I-kappa B Kinase - antagonists & inhibitors</subject><subject>Lipopolysaccharide</subject><subject>Lipopolysaccharide Receptors - genetics</subject><subject>Lipopolysaccharide Receptors - metabolism</subject><subject>lipopolysaccharides</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Lymphocyte Antigen 96 - genetics</subject><subject>Lymphocyte Antigen 96 - metabolism</subject><subject>Mice</subject><subject>NF-kappa B - metabolism</subject><subject>NFκB</subject><subject>Phosphoproteins - metabolism</subject><subject>Progesterone - biosynthesis</subject><subject>Pyridines - pharmacology</subject><subject>Rats</subject><subject>reverse transcriptase polymerase chain reaction</subject><subject>secretion</subject><subject>signal transduction</subject><subject>Signal Transduction - drug effects</subject><subject>Steroidogenesis</subject><subject>TLR-4</subject><subject>Toll-Like Receptor 4 - genetics</subject><subject>Toll-Like Receptor 4 - metabolism</subject><subject>transcription factor NF-kappa B</subject><subject>Transcription, Genetic - drug effects</subject><subject>Y1 cells</subject><issn>0303-7207</issn><issn>1872-8057</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEFuEzEUQC1ERUPhAGzAO1aTftszY1esIKItUkQXUImd5bH_BEcz9mBPImXFvTgEZ8JpCktWlv2fn74eIa8YLBmw9nK7HC0uORzvfAmifUIWTEleKWjkU7IAAaKSHOQ5eZ7zFgBkw9Uzcs6ZAGCiWZCfaz_FKQ6HbKz9bpJ3SPPsx91gZszUuITBDOUJU_QubjBg9pn6QFN0GGZqcRgy7Q7U0M_Xv399qBxOGB5GIxZj8Hks-D4Oex82dHX3reLU2NnvzexjeEHOejNkfPl4XpD7649fV7fV-u7m0-r9urJCtnPFOylBdKJprhplTSdr09reWccNdKJ2ktUWe5QSr3qJ2PcFVaq1YGRjatGKC_L25J1S_LHDPOvR5-PuJmDcZa1axkE1iheSnUibYs4Jez0lP5p00Az0Mbve6pJdH7NrxjU82F8_2nfdiO7fj7-dC_DmBPQmarNJPuv7L8XQlLGCthaFeHcisFTYe0w6W4_BovMJ7axd9P9Z4A9-ep9n</recordid><startdate>20110430</startdate><enddate>20110430</enddate><creator>Martinez Calejman, C.</creator><creator>Astort, F.</creator><creator>Di Gruccio, J.M.</creator><creator>Repetto, E.M.</creator><creator>Mercau, M.</creator><creator>Giordanino, E.</creator><creator>Sanchez, R.</creator><creator>Pignataro, O.</creator><creator>Arias, P.</creator><creator>Cymeryng, C.B.</creator><general>Elsevier Ireland Ltd</general><scope>FBQ</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></search><sort><creationdate>20110430</creationdate><title>Lipopolysaccharide stimulates adrenal steroidogenesis in rodent cells by a NFκB-dependent mechanism involving COX-2 activation</title><author>Martinez Calejman, C. ; Astort, F. ; Di Gruccio, J.M. ; Repetto, E.M. ; Mercau, M. ; Giordanino, E. ; Sanchez, R. ; Pignataro, O. ; Arias, P. ; Cymeryng, C.B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c376t-2b7703b355958cab74a6cfdcd2a0b34d714cefe77e9f7eeffb35886c0a75a4363</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adrenal cortex</topic><topic>Adrenal Glands - cytology</topic><topic>Adrenal Glands - enzymology</topic><topic>Adrenal Glands - metabolism</topic><topic>Animals</topic><topic>Cell Culture Techniques</topic><topic>Cell Line, Tumor</topic><topic>Corticosterone - biosynthesis</topic><topic>Cyclooxygenase 2 - metabolism</topic><topic>Cyclooxygenase-2</topic><topic>cytokines</topic><topic>Enzyme Activation - drug effects</topic><topic>Heterocyclic Compounds, 3-Ring - pharmacology</topic><topic>I-kappa B Kinase - antagonists & inhibitors</topic><topic>Lipopolysaccharide</topic><topic>Lipopolysaccharide Receptors - genetics</topic><topic>Lipopolysaccharide Receptors - metabolism</topic><topic>lipopolysaccharides</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>Lymphocyte Antigen 96 - genetics</topic><topic>Lymphocyte Antigen 96 - metabolism</topic><topic>Mice</topic><topic>NF-kappa B - metabolism</topic><topic>NFκB</topic><topic>Phosphoproteins - metabolism</topic><topic>Progesterone - biosynthesis</topic><topic>Pyridines - pharmacology</topic><topic>Rats</topic><topic>reverse transcriptase polymerase chain reaction</topic><topic>secretion</topic><topic>signal transduction</topic><topic>Signal Transduction - drug effects</topic><topic>Steroidogenesis</topic><topic>TLR-4</topic><topic>Toll-Like Receptor 4 - genetics</topic><topic>Toll-Like Receptor 4 - metabolism</topic><topic>transcription factor NF-kappa B</topic><topic>Transcription, Genetic - drug effects</topic><topic>Y1 cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Martinez Calejman, C.</creatorcontrib><creatorcontrib>Astort, F.</creatorcontrib><creatorcontrib>Di Gruccio, J.M.</creatorcontrib><creatorcontrib>Repetto, E.M.</creatorcontrib><creatorcontrib>Mercau, M.</creatorcontrib><creatorcontrib>Giordanino, E.</creatorcontrib><creatorcontrib>Sanchez, R.</creatorcontrib><creatorcontrib>Pignataro, O.</creatorcontrib><creatorcontrib>Arias, P.</creatorcontrib><creatorcontrib>Cymeryng, C.B.</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular and cellular endocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Martinez Calejman, C.</au><au>Astort, F.</au><au>Di Gruccio, J.M.</au><au>Repetto, E.M.</au><au>Mercau, M.</au><au>Giordanino, E.</au><au>Sanchez, R.</au><au>Pignataro, O.</au><au>Arias, P.</au><au>Cymeryng, C.B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lipopolysaccharide stimulates adrenal steroidogenesis in rodent cells by a NFκB-dependent mechanism involving COX-2 activation</atitle><jtitle>Molecular and cellular endocrinology</jtitle><addtitle>Mol Cell Endocrinol</addtitle><date>2011-04-30</date><risdate>2011</risdate><volume>337</volume><issue>1</issue><spage>1</spage><epage>6</epage><pages>1-6</pages><issn>0303-7207</issn><eissn>1872-8057</eissn><abstract>Stimulation of adrenal steroidogenesis is involved in the HPA response to exogenous noxa. Although inflammatory cytokines can mediate the LPS-triggered activation of the HPA, direct effects of LPS on glucocorticoid release have been described. Present studies were undertaken to characterize the molecular mechanisms underlying the effect of LPS on steroid secretion in isolated rodent adrenal cells, assessing the participation of NFκB and COX-2 activities in this response.
Our results show that LPS treatment stimulates steroidogenesis in murine and rat adrenocortical cells, and that Y1 cells express the binding-transducing complex TLR-4/CD14/MD-2, as demonstrated by RT-PCR. NFκB activity and COX-2 protein levels are increased in this cell line by LPS treatment, and pharmacologic and molecular manipulation of the NFκB pathway significantly affected both COX-2 protein levels and steroid production. Finally, pharmacological inhibition of COX-2 activity significantly impairs steroid production. Thus, our results strongly suggest that the mechanism involved in the stimulation of steroidogenesis by LPS in rodent adrenal cells involves the activation of the NFκB signaling pathway and the induction of COX-2.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>21300135</pmid><doi>10.1016/j.mce.2010.12.036</doi><tpages>6</tpages></addata></record> |
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| subjects | Adrenal cortex Adrenal Glands - cytology Adrenal Glands - enzymology Adrenal Glands - metabolism Animals Cell Culture Techniques Cell Line, Tumor Corticosterone - biosynthesis Cyclooxygenase 2 - metabolism Cyclooxygenase-2 cytokines Enzyme Activation - drug effects Heterocyclic Compounds, 3-Ring - pharmacology I-kappa B Kinase - antagonists & inhibitors Lipopolysaccharide Lipopolysaccharide Receptors - genetics Lipopolysaccharide Receptors - metabolism lipopolysaccharides Lipopolysaccharides - pharmacology Lymphocyte Antigen 96 - genetics Lymphocyte Antigen 96 - metabolism Mice NF-kappa B - metabolism NFκB Phosphoproteins - metabolism Progesterone - biosynthesis Pyridines - pharmacology Rats reverse transcriptase polymerase chain reaction secretion signal transduction Signal Transduction - drug effects Steroidogenesis TLR-4 Toll-Like Receptor 4 - genetics Toll-Like Receptor 4 - metabolism transcription factor NF-kappa B Transcription, Genetic - drug effects Y1 cells |
| title | Lipopolysaccharide stimulates adrenal steroidogenesis in rodent cells by a NFκB-dependent mechanism involving COX-2 activation |
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