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Human host defense peptide LL-37 facilitates double-stranded RNA pro-inflammatory signaling through up-regulation of TLR3 expression in vascular smooth muscle cells
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- Dahl, Sara (author)
- Lund University,Lunds universitet,Kärlfysiologi,Forskargrupper vid Lunds universitet,Vascular Physiology,Lund University Research Groups
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- Cerps, Samuel (author)
- Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups
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- Rippe, Catarina (author)
- Lund University,Lunds universitet,Cellulär biomekanik,Forskargrupper vid Lunds universitet,Cellular Biomechanics,Lund University Research Groups
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- Swärd, Karl (author)
- Lund University,Lunds universitet,Cellulär biomekanik,Forskargrupper vid Lunds universitet,Cellular Biomechanics,Lund University Research Groups
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- Uller, Lena (author)
- Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups
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- Svensson, Daniel (author)
- Karolinska Institutet,Lund University,Lunds universitet,Centrum för analys och syntes,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Centre for Analysis and Synthesis,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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- Nilsson, Bengt-Olof (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Kärlfysiologi,Forskargrupper vid Lunds universitet,Department of Experimental Medical Science,Faculty of Medicine,Vascular Physiology,Lund University Research Groups
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(creator_code:org_t)
- 2020-03-27
- 2020
- English.
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In: Inflammation Research. - : Springer Science and Business Media LLC. - 1420-908X .- 1023-3830. ; 69:6, s. 579-588
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Abstract
Subject headings
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- OBJECTIVE: The importance of human host defense peptide LL-37 in vascular innate immunity is not understood. Here, we assess the impact of LL-37 on double-stranded RNA (dsRNA) signaling in human vascular smooth muscle cells.MATERIALS AND METHODS: Cellular import of LL-37 and synthetic dsRNA (poly I:C) were investigated by immunocytochemistry and fluorescence imaging. Transcript and protein expression were determined by qPCR, ELISA and Western blot. Knockdown of TLR3 was performed by siRNA.RESULTS: LL-37 was rapidly internalized, suggesting that it has intracellular actions. Co-stimulation with poly I:C and LL-37 enhanced pro-inflammatory IL-6 and MCP-1 transcripts several fold compared to treatment with poly I:C or LL-37 alone. Poly I:C increased IL-6 and MCP-1 protein production, and this effect was potentiated by LL-37. LL-37-induced stimulation of poly I:C signaling was not associated with enhanced import of poly I:C. Treatment with poly I:C and LL-37 in combination increased expression of dsRNA receptor TLR3 compared to stimulation with poly I:C or LL-37 alone. In TLR3 knockdown cells, treatment with poly I:C and LL-37 in combination had no effect on IL-6 and MCP-1 expression, showing loss of function.CONCLUSIONS: LL-37 potentiates dsRNA-induced cytokine production through up-regulation of TLR3 expression representing a novel pro-inflammatory mechanism.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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