Schistosome infection-derived Hepatic Stellate Cells are cellular source of prostaglandin D-2: Role in TGF-beta-stimulated VEGF production

作者：Paiva Ligia Almeida^*; Coelho Karen Almeida; Luna Gomes Tatiana; El Cheikh Marcia Cury; Borojevic Radovan; Perez Sandra Aurora; Bozza Patricia Torres; Bandeira Melo Christianne

来源：Prostaglandins, Leukotrienes and Essential Fatty Acids, 2015, 95: 57-62.

DOI：10.1016/j.plefa.2015.01.004

• Hepatic Stellate Cells
• Prostaglandin D-2
• VEGF
• S. mansoni
• Eosinophil

Hepatic Stellate Cells (HSCs) play a crucial role in pathogenesis of liver inflammation and fibrosis. During chronic liver injury, HSCs lose vitamin A and transform into myofibroblastic cells. In schistosomal granulomas, these activated HSCs are called GR-HSCs. Schistosomal-triggered hepatic fibrogenesis has TGF-beta as the most potent fibrogenic stimulus, that also controls gene expression of the angiogenic molecule VEGF in HSCs. COX-dependent production of prostaglandins (PGs) also play role in angiogenic processes. Besides angiogenic roles, prostanoids control immunomodulation of Schistosoma mansoni infection. Specifically, schistosoma-derived PGD(2) has emerged as a key parasite regulator of immune defense evasion, while no role is still established to host PGD(2). Therefore, the aim of this work is to investigate the ability of GR-HSCs to synthesize COX-derived PGD(2) and a potential role of this prostanoid in VEGF production by GR-HSCs in vitro. Here, we confirmed that GR-HSCs express COX-2, which displayed perinuclear localization. While unstimulated GR-HSCs produce basal levels of PGD(2), TGF-P stimulation besides increasing COX2- mRNA levels, enhanced synthesis/secretion of PGD(2) in GR-HSCs supernatant. Moreover, GR-HSCs-derived PGD(2) mediate VEGF production by TGF-beta-stimulated GR-HSCs, since the pre-treatment with HQL-79, an inhibitor of hematopoietic PGD synthase inhibited both PGD2 synthesis and VEGF secretion by TGF-beta-stimulated GR-HSCs. All together, our findings show an autocrine/paracrine activity of GR-HSCs-derived PGD(2) on TGF-beta-induced VEGF production by GR-HSCs, unveiling a role for PGD(2) as important regulator of HSCs activation in hepatic granulomas from schistosome infected mice.

• 出版日期2015-4