Type I Cystatin Derived from <i>Fasciola gigantica</i> Suppresses Macrophage-Mediated Inflammatory Responses
There is an inverse relationship between the high incidence of helminth infection and the low incidence of inflammatory disease. Hence, it may be that helminth molecules have anti-inflammatory effects. Helminth cystatins are being extensively studied for anti-inflammatory potential. Therefore, in th...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/12/3/395 |
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| author | Pathanin Chantree Mayuri Tarasuk Parisa Prathaphan Jittiporn Ruangtong Mantana Jamklang Sirilak Chumkiew Pongsakorn Martviset |
| author_facet | Pathanin Chantree Mayuri Tarasuk Parisa Prathaphan Jittiporn Ruangtong Mantana Jamklang Sirilak Chumkiew Pongsakorn Martviset |
| author_sort | Pathanin Chantree |
| collection | DOAJ |
| description | There is an inverse relationship between the high incidence of helminth infection and the low incidence of inflammatory disease. Hence, it may be that helminth molecules have anti-inflammatory effects. Helminth cystatins are being extensively studied for anti-inflammatory potential. Therefore, in this study, the recombinant type I cystatin (stefin-1) of <i>Fasciola gigantica</i> (rFgCyst) was verified to have LPS-activated anti-inflammatory potential, including in human THP-1-derived macrophages and RAW 264.7 murine macrophages. The results from the MTT assay suggest that rFgCyst did not alter cell viability; moreover, it exerted anti-inflammatory activity by decreasing the production of proinflammatory cytokines and mediators, including IL-1β, IL-6, IL-8, TNF-α, iNOS, and COX-2 at the gene transcription and protein expression levels, as determined by qRT-PCR and Western blot analysis, respectively. Further, the secretion levels of IL-1β, IL-6, and TNF-α determined by ELISA and the NO production level determined by the Griess test were decreased. Furthermore, in Western blot analysis, the anti-inflammatory effects involved the downregulation of pIKKα/β, pIκBα, and pNF-κB in the NF-κB signaling pathway, hence reducing the translocation from the cytosol into the nucleus of pNF-κB, which subsequently turned on the gene of proinflammatory molecules. Therefore, cystatin type 1 of <i>F. gigantica</i> is a potential candidate for inflammatory disease treatment. |
| first_indexed | 2024-03-11T06:03:02Z |
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| language | English |
| last_indexed | 2024-03-11T06:03:02Z |
| publishDate | 2023-03-01 |
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| series | Pathogens |
| spelling | doaj.art-3438a2adb40444cfbb637383e80dc0fa2023-11-17T13:09:23ZengMDPI AGPathogens2076-08172023-03-0112339510.3390/pathogens12030395Type I Cystatin Derived from <i>Fasciola gigantica</i> Suppresses Macrophage-Mediated Inflammatory ResponsesPathanin Chantree0Mayuri Tarasuk1Parisa Prathaphan2Jittiporn Ruangtong3Mantana Jamklang4Sirilak Chumkiew5Pongsakorn Martviset6Department of Preclinical Science, Faculty of Medicine, Thammasat University, Pathumthani 12120, ThailandGraduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Pathumthani 12120, ThailandThammasat University Research Unit in Nutraceuticals and Food Safety, Thammasat University, Pathumthani 12120, ThailandThammasat University Research Unit in Nutraceuticals and Food Safety, Thammasat University, Pathumthani 12120, ThailandInstitute of Science, Suranaree University of Technology, Nakhon Ratchasima 30000, ThailandInstitute of Science, Suranaree University of Technology, Nakhon Ratchasima 30000, ThailandDepartment of Preclinical Science, Faculty of Medicine, Thammasat University, Pathumthani 12120, ThailandThere is an inverse relationship between the high incidence of helminth infection and the low incidence of inflammatory disease. Hence, it may be that helminth molecules have anti-inflammatory effects. Helminth cystatins are being extensively studied for anti-inflammatory potential. Therefore, in this study, the recombinant type I cystatin (stefin-1) of <i>Fasciola gigantica</i> (rFgCyst) was verified to have LPS-activated anti-inflammatory potential, including in human THP-1-derived macrophages and RAW 264.7 murine macrophages. The results from the MTT assay suggest that rFgCyst did not alter cell viability; moreover, it exerted anti-inflammatory activity by decreasing the production of proinflammatory cytokines and mediators, including IL-1β, IL-6, IL-8, TNF-α, iNOS, and COX-2 at the gene transcription and protein expression levels, as determined by qRT-PCR and Western blot analysis, respectively. Further, the secretion levels of IL-1β, IL-6, and TNF-α determined by ELISA and the NO production level determined by the Griess test were decreased. Furthermore, in Western blot analysis, the anti-inflammatory effects involved the downregulation of pIKKα/β, pIκBα, and pNF-κB in the NF-κB signaling pathway, hence reducing the translocation from the cytosol into the nucleus of pNF-κB, which subsequently turned on the gene of proinflammatory molecules. Therefore, cystatin type 1 of <i>F. gigantica</i> is a potential candidate for inflammatory disease treatment.https://www.mdpi.com/2076-0817/12/3/395stefin-1liver flukeanti-inflammationTHP-1RAW 264.7NF-κB |
| spellingShingle | Pathanin Chantree Mayuri Tarasuk Parisa Prathaphan Jittiporn Ruangtong Mantana Jamklang Sirilak Chumkiew Pongsakorn Martviset Type I Cystatin Derived from <i>Fasciola gigantica</i> Suppresses Macrophage-Mediated Inflammatory Responses Pathogens stefin-1 liver fluke anti-inflammation THP-1 RAW 264.7 NF-κB |
| title | Type I Cystatin Derived from <i>Fasciola gigantica</i> Suppresses Macrophage-Mediated Inflammatory Responses |
| title_full | Type I Cystatin Derived from <i>Fasciola gigantica</i> Suppresses Macrophage-Mediated Inflammatory Responses |
| title_fullStr | Type I Cystatin Derived from <i>Fasciola gigantica</i> Suppresses Macrophage-Mediated Inflammatory Responses |
| title_full_unstemmed | Type I Cystatin Derived from <i>Fasciola gigantica</i> Suppresses Macrophage-Mediated Inflammatory Responses |
| title_short | Type I Cystatin Derived from <i>Fasciola gigantica</i> Suppresses Macrophage-Mediated Inflammatory Responses |
| title_sort | type i cystatin derived from i fasciola gigantica i suppresses macrophage mediated inflammatory responses |
| topic | stefin-1 liver fluke anti-inflammation THP-1 RAW 264.7 NF-κB |
| url | https://www.mdpi.com/2076-0817/12/3/395 |
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