BACKGROUND: The antimicrobial peptide PR39 is a porcine cathelicidin with angiogenic and antiapoptotic activities, as it can regulate the expression of vascular endothelial growth factor (VEGF) and inhibitor apoptosis protein-2 (c-IAP-2) in endothelial cells. The human homolog LL-37 has been found to be highly expressed in human keratinocytes from psoriatic patients, but it is not known whether LL-37 can modulate the expression of VEGF and c-IAP-2 in keratinocytes, as both molecules are involved in the overgrowth of psoriatic skin. Therefore, in this work, we studied the possible role of CAP18/LL-37 in the modulation of VEGF and c-IAP-2 expression in human keratinocytes. METHODS: The CAP18/LL-37 gene was cloned into a plasmid that contained green fluorescent protein (GFP). This plasmid was called pGFP-CAP18/LL-37. The expression of LL-37, VEGF, and c-IAP-2 was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting in HaCaT cells transfected with pGFP-CAP18/LL-37. Specific DNAzymes were used to break the CAP18/LL-37 mRNA (DNAz-CAP18/LL-37). RESULTS: HaCaT cells transfected with pGFP-CAP18/LL-37 showed the upregulation of VEGF and c-IAP-2 mRNAs. Hypoxia-inducible factor-1alpha (HIF-1alpha) mRNA expression did not change during the assays; however, its protein was increased, as well as the VEGF protein. HaCaT cells cotransfected with pGFP-CAP18/LL-37 and DNAz-CAP18/LL-37 showed depleted expression of LL-37, VEGF, and c-IAP-2 mRNAs. CONCLUSIONS: These results suggest that LL-37 may modulate the expression of VEGF and c-IAP-2 via HIF-1alpha in human keratinocytes.
BACKGROUND: The antimicrobial peptide PR39 is a porcine cathelicidin with angiogenic and antiapoptotic activities, as it can regulate the expression of vascular endothelial growth factor (VEGF) and inhibitor apoptosis protein-2 (c-IAP-2) in endothelial cells. The human homolog LL-37 has been found to be highly expressed in human keratinocytes from psoriaticpatients, but it is not known whether LL-37 can modulate the expression of VEGF and c-IAP-2 in keratinocytes, as both molecules are involved in the overgrowth of psoriatic skin. Therefore, in this work, we studied the possible role of CAP18/LL-37 in the modulation of VEGF and c-IAP-2 expression in human keratinocytes. METHODS: The CAP18/LL-37 gene was cloned into a plasmid that contained green fluorescent protein (GFP). This plasmid was called pGFP-CAP18/LL-37. The expression of LL-37, VEGF, and c-IAP-2 was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting in HaCaT cells transfected with pGFP-CAP18/LL-37. Specific DNAzymes were used to break the CAP18/LL-37 mRNA (DNAz-CAP18/LL-37). RESULTS: HaCaT cells transfected with pGFP-CAP18/LL-37 showed the upregulation of VEGF and c-IAP-2 mRNAs. Hypoxia-inducible factor-1alpha (HIF-1alpha) mRNA expression did not change during the assays; however, its protein was increased, as well as the VEGF protein. HaCaT cells cotransfected with pGFP-CAP18/LL-37 and DNAz-CAP18/LL-37 showed depleted expression of LL-37, VEGF, and c-IAP-2 mRNAs. CONCLUSIONS: These results suggest that LL-37 may modulate the expression of VEGF and c-IAP-2 via HIF-1alpha in human keratinocytes.
Authors: Lars Steinstraesser; Martin C Lam; Frank Jacobsen; Paolo E Porporato; Kiran Kumar Chereddy; Mustafa Becerikli; Ingo Stricker; Robert Ew Hancock; Marcus Lehnhardt; Pierre Sonveaux; Véronique Préat; Gaëlle Vandermeulen Journal: Mol Ther Date: 2013-12-05 Impact factor: 11.454
Authors: Azael Torales-Cardeña; Isaí Martínez-Torres; Sandra Rodríguez-Martínez; Fernando Gómez-Chávez; Juan C Cancino-Díaz; Ernesto A Vázquez-Sánchez; Mario E Cancino-Díaz Journal: Mediators Inflamm Date: 2015-06-07 Impact factor: 4.711
Authors: Günther Weber; Clara Ibel Chamorro; Fredrik Granath; Annelie Liljegren; Sami Zreika; Zuzana Saidak; Bengt Sandstedt; Samuel Rotstein; Romuald Mentaverri; Fabio Sánchez; Andor Pivarcsi; Mona Ståhle Journal: Breast Cancer Res Date: 2009-01-30 Impact factor: 6.466