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. 2017 Aug 8;7:7563. doi: 10.1038/s41598-017-07610-0

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

PMC Copyright notice

Acetylated PGP increases vascular ET-1 production via CXCR2 in vivo. (a) As proof of concept, serum concentrations for PGP were measured from c57bl/6 mice systemically treated with PBS, PGG, IL-8 or PGP. Importantly, intraperitoneal administration of PGP increased circulating serum PGP to concentrations comparable to patient samples (*^#! P < 0.0001, F = 23.2, n = 4 animals per experimental group). (b) Intraperitoneal administration of IL-8 or PGP to c57bl/6 mice significantly increased serum ET1 when compared to PBS and PGG treated mice (*^# P < 0.0001 compared to PBS and PGG, F = 13.07, n = 8 animals per group). (c) Direct measurement of ET1 in aortic tissue lysates revealed similar results with significant increases in tissue specific ET1 (*^# P < 0.0001, F = 24.7, n = 8 animals per group) and (d) big ET1 production (*^# P < 0.0001, F = 18.5, n = 8 animals per group). (e) Intraperitoneal administration of both IL-8 and PGP significantly increased aortic transcription of Endothelin 1 gene (EDN1) mRNA in vivo (*^# P = 0.03 compared to PBS and PGG, F = 5.2, n = 5 animals per group). Co-administration of PGP and SB225002 (1 mg/kg) blocked the effects of PGP alone on (f) aortic ET1 production (*^#! P = 0.01 compared to PBS, SB225002, and PGP + SB225002, F = 5.7, n = 8 animals per group) and (g) serum ET1 concentrations (*P = 0.02 compared to SB225002 and ^# P < 0.001 compared to PGP + SB225002, F = 5.7, n = 5 animals per group). These results demonstrate the importance of CXCR2 activation in ET1 production in vivo.