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Label-free quantita...
Label-free quantitative mass spectrometry reveals novel pathways involved in LL-37 expression
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Cederlund, A (författare)
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- Nylen, F (författare)
- Karolinska Institutet
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- Miraglia, E (författare)
- Karolinska Institutet
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- Bergman, P (författare)
- Karolinska Institutet
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Gudmundsson, GH (författare)
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- Agerberth, B (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2013-11-16
- 2014
- Engelska.
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Ingår i: Journal of innate immunity. - : S. Karger AG. - 1662-8128 .- 1662-811X. ; 6:3, s. 365-376
- Relaterad länk:
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https://europepmc.or...
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http://kipublication...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
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