Clonorchis sinensis lysophospholipase A upregulates IL-25 expression in macrophages as a potential pathway to liver fibrosis
Abstract Background Liver fibrosis is an excessive wound-healing reaction that requires the participation of inflammatory cells and hepatic stellate cells (HSCs). The pathogenesis of liver fibrosis caused by viruses and alcohol has been well characterized, but the molecular mechanisms underlying liv...
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| Format: | Article |
| Language: | English |
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BMC
2017-06-01
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| Series: | Parasites & Vectors |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13071-017-2228-z |
| _version_ | 1818821517809549312 |
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| author | Lina Zhou Mengchen Shi Lu Zhao Zhipeng Lin Zeli Tang Hengchang Sun Tingjin Chen Zhiyue Lv Jin Xu Yan Huang Xinbing Yu |
| author_facet | Lina Zhou Mengchen Shi Lu Zhao Zhipeng Lin Zeli Tang Hengchang Sun Tingjin Chen Zhiyue Lv Jin Xu Yan Huang Xinbing Yu |
| author_sort | Lina Zhou |
| collection | DOAJ |
| description | Abstract Background Liver fibrosis is an excessive wound-healing reaction that requires the participation of inflammatory cells and hepatic stellate cells (HSCs). The pathogenesis of liver fibrosis caused by viruses and alcohol has been well characterized, but the molecular mechanisms underlying liver fibrosis induced by the liver fluke Clonorchis sinensis are poorly understood. Lysophospholipase A (LysoPLA), which deacylates lysophospholipids, plays a critical role in mediating the virulence and pathogenesis of parasites and fungi; however, the roles of C. sinensis lysophospholipase A (CsLysoPLA) in C. sinensis-induced liver fibrosis remain unknown. Methods A mouse macrophage cell line (RAW264.7) was cultured and treated with CsLysoPLA. IL-25 and members of its associated signaling pathway were detected by performing quantitative real-time PCR, Western blotting and immunofluorescent staining. A human hepatic stellate cell line (LX-2) was cultured and exposed to IL-25. LX-2 cell activation markers were examined via quantitative real-time PCR, Western blotting and immunofluorescent staining. Migration was analyzed in transwell plates. Results Treating RAW264.7 cells with CsLysoPLA significantly induced IL-25 expression. Elevated PKA, B-Raf, and ERK1/2 mRNA levels and phosphorylated B-Raf and ERK1/2 were detected in CsLysoPLA-stimulated RAW264.7 cells. The PKA inhibitor H-89 weakened B-Raf and ERK1/2 phosphorylation whereas the AKT activator SC79 attenuated ERK1/2 phosphorylation in RAW264.7 cells. Both H-89 and SC79 inhibited CsLysoPLA-induced IL-25 upregulation. In addition, stimulation of LX-2 cells with IL-25 upregulated the expression of mesenchymal cell markers, including α-smooth muscle actin (α-SMA) and collagen type I (Collagen-I), and promoted cell migration. Conclusions CsLysoPLA activates HSCs by upregulating IL-25 in macrophages through the PKA-dependent B-Raf/ERK1/2 pathway and potentially promotes hepatic fibrosis during C. sinensis infection. |
| first_indexed | 2024-12-18T23:09:27Z |
| format | Article |
| id | doaj.art-262acb183e6f44c08b765e5b98ace77a |
| institution | Directory Open Access Journal |
| issn | 1756-3305 |
| language | English |
| last_indexed | 2024-12-18T23:09:27Z |
| publishDate | 2017-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Parasites & Vectors |
| spelling | doaj.art-262acb183e6f44c08b765e5b98ace77a2022-12-21T20:48:23ZengBMCParasites & Vectors1756-33052017-06-0110111010.1186/s13071-017-2228-zClonorchis sinensis lysophospholipase A upregulates IL-25 expression in macrophages as a potential pathway to liver fibrosisLina Zhou0Mengchen Shi1Lu Zhao2Zhipeng Lin3Zeli Tang4Hengchang Sun5Tingjin Chen6Zhiyue Lv7Jin Xu8Yan Huang9Xinbing Yu10Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen UniversityDepartment of Parasitology, Zhongshan School of Medicine, Sun Yat-sen UniversityDepartment of Parasitology, Zhongshan School of Medicine, Sun Yat-sen UniversityDepartment of Parasitology, Zhongshan School of Medicine, Sun Yat-sen UniversityDepartment of Parasitology, Zhongshan School of Medicine, Sun Yat-sen UniversityDepartment of Parasitology, Zhongshan School of Medicine, Sun Yat-sen UniversityDepartment of Parasitology, Zhongshan School of Medicine, Sun Yat-sen UniversityDepartment of Parasitology, Zhongshan School of Medicine, Sun Yat-sen UniversityDepartment of Parasitology, Zhongshan School of Medicine, Sun Yat-sen UniversityDepartment of Parasitology, Zhongshan School of Medicine, Sun Yat-sen UniversityDepartment of Parasitology, Zhongshan School of Medicine, Sun Yat-sen UniversityAbstract Background Liver fibrosis is an excessive wound-healing reaction that requires the participation of inflammatory cells and hepatic stellate cells (HSCs). The pathogenesis of liver fibrosis caused by viruses and alcohol has been well characterized, but the molecular mechanisms underlying liver fibrosis induced by the liver fluke Clonorchis sinensis are poorly understood. Lysophospholipase A (LysoPLA), which deacylates lysophospholipids, plays a critical role in mediating the virulence and pathogenesis of parasites and fungi; however, the roles of C. sinensis lysophospholipase A (CsLysoPLA) in C. sinensis-induced liver fibrosis remain unknown. Methods A mouse macrophage cell line (RAW264.7) was cultured and treated with CsLysoPLA. IL-25 and members of its associated signaling pathway were detected by performing quantitative real-time PCR, Western blotting and immunofluorescent staining. A human hepatic stellate cell line (LX-2) was cultured and exposed to IL-25. LX-2 cell activation markers were examined via quantitative real-time PCR, Western blotting and immunofluorescent staining. Migration was analyzed in transwell plates. Results Treating RAW264.7 cells with CsLysoPLA significantly induced IL-25 expression. Elevated PKA, B-Raf, and ERK1/2 mRNA levels and phosphorylated B-Raf and ERK1/2 were detected in CsLysoPLA-stimulated RAW264.7 cells. The PKA inhibitor H-89 weakened B-Raf and ERK1/2 phosphorylation whereas the AKT activator SC79 attenuated ERK1/2 phosphorylation in RAW264.7 cells. Both H-89 and SC79 inhibited CsLysoPLA-induced IL-25 upregulation. In addition, stimulation of LX-2 cells with IL-25 upregulated the expression of mesenchymal cell markers, including α-smooth muscle actin (α-SMA) and collagen type I (Collagen-I), and promoted cell migration. Conclusions CsLysoPLA activates HSCs by upregulating IL-25 in macrophages through the PKA-dependent B-Raf/ERK1/2 pathway and potentially promotes hepatic fibrosis during C. sinensis infection.http://link.springer.com/article/10.1186/s13071-017-2228-zCsLysoPLALiver fibrosisIL-25 |
| spellingShingle | Lina Zhou Mengchen Shi Lu Zhao Zhipeng Lin Zeli Tang Hengchang Sun Tingjin Chen Zhiyue Lv Jin Xu Yan Huang Xinbing Yu Clonorchis sinensis lysophospholipase A upregulates IL-25 expression in macrophages as a potential pathway to liver fibrosis Parasites & Vectors CsLysoPLA Liver fibrosis IL-25 |
| title | Clonorchis sinensis lysophospholipase A upregulates IL-25 expression in macrophages as a potential pathway to liver fibrosis |
| title_full | Clonorchis sinensis lysophospholipase A upregulates IL-25 expression in macrophages as a potential pathway to liver fibrosis |
| title_fullStr | Clonorchis sinensis lysophospholipase A upregulates IL-25 expression in macrophages as a potential pathway to liver fibrosis |
| title_full_unstemmed | Clonorchis sinensis lysophospholipase A upregulates IL-25 expression in macrophages as a potential pathway to liver fibrosis |
| title_short | Clonorchis sinensis lysophospholipase A upregulates IL-25 expression in macrophages as a potential pathway to liver fibrosis |
| title_sort | clonorchis sinensis lysophospholipase a upregulates il 25 expression in macrophages as a potential pathway to liver fibrosis |
| topic | CsLysoPLA Liver fibrosis IL-25 |
| url | http://link.springer.com/article/10.1186/s13071-017-2228-z |
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