BACKGROUND: Interleukin-17 (IL-17) has been cast as a major player in angiopoiesis of carcinoma, but its role in hepatic haemangioma is not entirely clear. AIM: The aim of this study is to address the expression levels and the molecular mechanism underlying the role of IL-17 on hepatic haemangioma progression. METHODS AND RESULTS: 20 hepatic haemangioma patients and 15 healthy subjects were included in this study. IL-17 mRNA levels were examined by PCR-based methods and protein levels by western blot. We observed a significant increase in tissue IL-17 mRNA and protein levels in hepatic haemangioma compared to normal liver tissue. Matrix metalloproteinase protein levels were slightly elevated in haemangiomas compared to normal, and IL-6 and phospho-stat3 levels were markedly elevated. However, no differences in mRNA levels of angiogenesis-associated cytokines such as vascular endothelial growth factor were seen in hepatic haemangiomas compared to normal cases taken from donor livers at the time of organ harvest. IL-17 was localised to CD4-positive cells by flow cytometry and to stromal cells and endothelial cells by immunohistochemistry. Owing to the absence of an animal model of haemangioma, we examined the effects of IL-17 on angiogenesis-related functions of vascular endothelial cells in vitro. Notably, IL-17, when added to cell cultures of human umbilical cord-derived endothelial cells, had an effect on the secretion of IL-6 and p-stat3. CONCLUSIONS: Based on these findings, we propose that IL-17 may mediate the angiogenesis in a IL-6-Stat3-dependent manner and play an important role in the pathophysiology of hepatic haemangioma.
BACKGROUND:Interleukin-17 (IL-17) has been cast as a major player in angiopoiesis of carcinoma, but its role in hepatic haemangioma is not entirely clear. AIM: The aim of this study is to address the expression levels and the molecular mechanism underlying the role of IL-17 on hepatic haemangioma progression. METHODS AND RESULTS: 20 hepatic haemangiomapatients and 15 healthy subjects were included in this study. IL-17 mRNA levels were examined by PCR-based methods and protein levels by western blot. We observed a significant increase in tissue IL-17 mRNA and protein levels in hepatic haemangioma compared to normal liver tissue. Matrix metalloproteinase protein levels were slightly elevated in haemangiomas compared to normal, and IL-6 and phospho-stat3 levels were markedly elevated. However, no differences in mRNA levels of angiogenesis-associated cytokines such as vascular endothelial growth factor were seen in hepatic haemangiomas compared to normal cases taken from donor livers at the time of organ harvest. IL-17 was localised to CD4-positive cells by flow cytometry and to stromal cells and endothelial cells by immunohistochemistry. Owing to the absence of an animal model of haemangioma, we examined the effects of IL-17 on angiogenesis-related functions of vascular endothelial cells in vitro. Notably, IL-17, when added to cell cultures of human umbilical cord-derived endothelial cells, had an effect on the secretion of IL-6 and p-stat3. CONCLUSIONS: Based on these findings, we propose that IL-17 may mediate the angiogenesis in a IL-6-Stat3-dependent manner and play an important role in the pathophysiology of hepatic haemangioma.
Authors: Stefan Thomann; Marcell Tóth; Simon David Sprengel; Jakob Liermann; Peter Schirmacher Journal: J Histochem Cytochem Date: 2022-07-09 Impact factor: 4.137