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Label-free quantita...
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Cederlund, A
(författare)
Label-free quantitative mass spectrometry reveals novel pathways involved in LL-37 expression
- Artikel/kapitelEngelska2014
Förlag, utgivningsår, omfång ...
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2013-11-16
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S. Karger AG,2014
Nummerbeteckningar
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LIBRIS-ID:oai:prod.swepub.kib.ki.se:128609648
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http://kipublications.ki.se/Default.aspx?queryparsed=id:128609648URI
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https://doi.org/10.1159/000355931DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Antimicrobial peptides are important for a healthy host-microbe homeostasis. In infections characterized by low levels of the human cathelicidin, LL-37, induction of its expression increases clearance of pathogens. Our aim was to discover signaling pathways and compounds capable of affecting the expression of LL-37. We recently observed a synergistic induction of LL-37 expression by stimulating the colonic epithelial cell-line HT-29 with lactose and phenylbutyrate (PBA). Here, we studied regulatory circuits mediating this synergism in HT-29 cells stimulated with lactose (60 g/l) and PBA (2 m<smlcap>M</smlcap>) for 24 h by using mass spectrometry and pathway analyses. Selected pathways were evaluated for their involvement in LL-37 regulation in a <i>CAMP</i> gene-luciferase reporter system. Three pathways were examined in detail: thyroid hormone receptor and retinoid X receptor (TR/RXR) activation, eicosanoid signaling and steroid biosynthesis. Induced expression of LL-37 was observed upon stimulation with triiodothyronine (T3, 2.5 n<smlcap>M</smlcap>-1 µ<smlcap>M</smlcap> for 3-30 h) and thyroxine (T4, 2.5-10 n<smlcap>M</smlcap> for 24 h). Furthermore, the synergism of lactose and PBA was reduced in cells coincubated with inhibitors of phospholipase A2, cyclooxygenase 2 or HMG-CoA reductase. Based on these results, we conclude that proteomics and pathway analyses are valuable tools for dissecting the regulatory networks involved in LL-37 expression.
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Nylen, FKarolinska Institutet
(författare)
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Miraglia, EKarolinska Institutet
(författare)
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Bergman, PKarolinska Institutet
(författare)
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Gudmundsson, GH
(författare)
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Agerberth, BKarolinska Institutet
(författare)
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Karolinska Institutet
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Journal of innate immunity: S. Karger AG6:3, s. 365-3761662-81281662-811X
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