Gene Profile of Chemokines on Hepatic Stellate Cells of Schistosome-Infected Mice and Antifibrotic Roles of CXCL9/10 on Liver Non-Parenchymal Cells

Abstract

Hepatic stellate cells (HSCs) play a key role in the development of liver fibrosis caused by schistosomiasis. Chemokines were widely expressed and involved in cellular activation, proliferation and migration in inflammatory and infectious diseases. However, little is known about the expressions of chemokines on HSCs in the schistosoma infection. In addition, the roles of chemokines in pathogenesis of liver fibrosis are not totally clear. In our study, we used microarray to analyze the temporal gene expressions of primary HSCs isolated from mice with both acute and chronic schistosomiasis. Our microarray data showed that most of the chemokines expressed on HSCs were upregulated at 3 weeks post-infection (p.i) when the egg granulomatous response was not obviously evoked in the liver. However, some of them like CXCL9, CXCL10 and CXCL11 were subsequently decreased at 6 weeks p.i when the granulomatous response reached the peak. In the chronic stage, most of the differentially expressed chemokines maintained persistent high-abundances. Furthermore, several chemokines including CCR2, CCR5, CCR7, CXCR3, CXCR4, CCL2, CCL5, CCL21, CXCL9 and CXCL10 were expressed by HCSs and the abundances of them were changed following the praziquantel treatment in the chronic stage, indicating that chemokines were possibly necessary for the persistence of the chronic stage. In vitro experiments, hepatic non-parenchymal cells, primary HSCs and human HSCs line LX-2 were stimulated by chemokines. The results showed that CXCL9 and CXCL10, but not CXCL11 or CXCL4, significantly inhibited the gene expressions of Col1α1, Col3α1 and α-SMA, indicating the potential anti-fibrosis effect of CXCL9 and CXCL10 in schistosomiasis. More interestingly, soluble egg antigen (SEA) of Schistosoma japonicum was able to inhibit transcriptional expressions of some chemokines by LX-2 cells, suggesting that SEA was capable of regulating the expression pattern of chemokine family and modulating the hepatic immune microenvironment in schistosomiasis.

Vascular endothelial growth factor promotes the activation of hepatic stellate cells in chronic schistosomiasis

“…PZQ treatment can reverse liver fibrosis in murine schistosomiasis 14 , 15 . Here we isolated the HSCs from both infected and PZQ‐treated mice and performed a microarray analysis 28 . As we expected, the transcript levels of MMP, TIMP and collagen were significantly decreased in the PZQ‐treated group (Table 1).…”

“…BABL/c mice ( n =10/group) were infected cutaneously with 12±2 S. japonicum cercariae and killed at 0, 3, 6, 12 and 18 weeks postinfection 14 , 28 . PZQ (Sigma‐Aldrich, St Louis, MO, USA) was suspended in 1% carboxymethyl cellulose and administered orally (250 mg per kg body weight per day) at 6 or 12 weeks postinfection for 3 days.…”

Predictive Value of Serum IFN-γ inducible Protein-10 and IFN-γ/IL-4 Ratio for Liver Fibrosis Progression in CHB Patients

“…This might explain why some contrasting results were obtained in the study of IP-10 on hepatic injury progression. Recently, Liang et al 40. have examined the roles for IP-10 in the development and progression of liver fibrosis using HSCs in vitro .…”

Vaccines and diagnostics for zoonotic schistosomiasis japonica

“…The Kato-Katz (KK) thick smear technique is the most widely used procedure, being the standard method recommended by the WHO for both qualitative and quantitative diagnoses of intestinal schistosomiasis. This leads to a marked underestimation of the prevalence and intensity of infection, particularly in low prevalence areas (Lier et al 2008), and this can confound confirmation of cure after PZQ treatment (Berhe et al 2004). Furthermore, if only a single KK slide is prepared from a single stool specimen, sensitivity is low (Lin et al 2011b).…”

“…While B cells suppress granulomatous pathology in schistosomiasis, it remains unclear whether these cells effect schistosome maturation, reproduction and granuloma development without the aid of CD4(+) T lymphocytes (Tang et al 2013). After egg deposition in tissues, the Th2 response becomes prominent, suggesting that egg antigens may directly inhibit the Th1 response (Liang et al 2012). Following cercarial infection, the early immune response is predominantly Th1, targeted at the adult worm.…”