| First Author | Paiva LA | Year | 2010 |
| Journal | Biochim Biophys Acta | Volume | 1801 |
| Issue | 12 | Pages | 1341-8 |
| PubMed ID | 20817008 | Mgi Jnum | J:170218 |
| Mgi Id | MGI:4944153 | Doi | 10.1016/j.bbalip.2010.08.014 |
| Citation | Paiva LA, et al. (2010) Interplay of cysteinyl leukotrienes and TGF-beta in the activation of hepatic stellate cells from Schistosoma mansoni granulomas. Biochim Biophys Acta 1801(12):1341-8 |
| abstractText | Hepatic stellate cells (HSCs) have a critical role in liver physiology, and in the pathogenesis of liver inflammation and fibrosis. Here, we investigated the interplay between leukotrienes (LT) and TGF-beta in the activation mechanisms of HSCs from schistosomal granulomas (GR-HSCs). First, we demonstrated that GR-HSCs express 5-lipoxygenase (5-LO), as detected by immunolocalization in whole cells and confirmed in cell lysates through western blotting and by mRNA expression through RT-PCR. Moreover, mRNA expression of 5-LO activating protein (FLAP) and LTC(4)-synthase was also documented, indicating that GR-HSCs have the molecular machinery required for LT synthesis. Morphological analysis of osmium and Oil-Red O-stained HSC revealed large numbers of small lipid droplets (also known as lipid bodies). We observed co-localization of lipid droplet protein marker (ADRP) and 5-LO by immunofluorescence microscopy. We demonstrated that GR-HSCs were able to spontaneously release cysteinyl-LTs (CysLTs), but not LTB(4,) into culture supernatants. CysLT production was highly enhanced after TGF-beta-stimulation. Moreover, the 5-LO inhibitor zileuton and 5-LO gene deletion were able to inhibit the TGF-beta-stimulated proliferation of GR-HSCs, suggesting a role for LTs in HSC activation. Here, we extend the immunoregulatory function of HSC by demonstrating that HSC from liver granulomas of schistosome-infected mouse are able to release Cys-LTs in a TGF-beta-regulated manner, potentially impacting pathogenesis and liver fibrosis in schistosomiasis. |
