Zhaorong Yue, Fei Xie, Ruyue Wang, Xin Wang, Hongyu Li
{"title":"连纳尔多肽通过上调细胞因子的产生并提高 CD4+、CD8+ 和 T 调节细胞的水平,减少小鼠模型中的免疫性血小板减少症。","authors":"Zhaorong Yue, Fei Xie, Ruyue Wang, Xin Wang, Hongyu Li","doi":"10.1089/jir.2024.0256","DOIUrl":null,"url":null,"abstract":"<p><p>Primary immune thrombocytopenia (ITP) is a condition marked by immune-mediated inadequate platelet production or excessive destruction. This study investigates the effects of Lienal polypeptide injection (LP) on T lymphocyte subgroups in the spleen and thymus, megakaryocyte counts in the bone marrow, and cytokine levels related to megakaryocyte development in mice with antibody-induced ITP, aiming to elucidate potential therapeutic mechanisms. We first assessed the effects of LP on Meg-01 megakaryocytic cells regarding proliferation, apoptosis, and differentiation using Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assays, Western blot analysis, and flow cytometry for apoptosis and CD41 expression as a differentiation marker. Following this, LP was administered intraperitoneally at 60 mg/(kg·d) for 11 days to ITP mice. We quantified peripheral blood platelets and bone marrow megakaryocytes, measured spleen and thymus indices, and assessed serum levels of stem cell factor (SCF), interleukin-3 (IL-3), interleukin-6 (IL-6), and platelet factor-4 (PF-4) via enzyme-linked immunosorbent assay (ELISA). Flow cytometry quantified T-helper cells (CD4<sup>+</sup>), cytotoxic T cells (CD8<sup>+</sup>), and regulatory T cells (Tregs). LP significantly induced apoptosis in Meg-01 cells while not markedly affecting differentiation. In ITP mice, LP effectively prevented platelet decline without affecting megakaryocyte counts or maturity. Increased SCF, IL-3, and IL-6 levels, alongside decreased PF-4 levels, correlated with enhanced platelet production. Moreover, CD4<sup>+</sup>/CD8<sup>+</sup> ratios and Treg populations increased, contributing to reduced platelet destruction. In conclusion, LP exerts a protective effect in ITP by modulating SCF, IL-3, IL-6, and PF-4 levels and restoring the balance of T cell subtypes, elucidating its therapeutic potential.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":""},"PeriodicalIF":1.9000,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Lienal Polypeptide Decreases Immune Thrombocytopenia in a Mouse Model by Upregulating Cytokine Production and Increasing the Levels of CD4<sup>+</sup>, CD8<sup>+</sup>, and T Regulatory Cells.\",\"authors\":\"Zhaorong Yue, Fei Xie, Ruyue Wang, Xin Wang, Hongyu Li\",\"doi\":\"10.1089/jir.2024.0256\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Primary immune thrombocytopenia (ITP) is a condition marked by immune-mediated inadequate platelet production or excessive destruction. This study investigates the effects of Lienal polypeptide injection (LP) on T lymphocyte subgroups in the spleen and thymus, megakaryocyte counts in the bone marrow, and cytokine levels related to megakaryocyte development in mice with antibody-induced ITP, aiming to elucidate potential therapeutic mechanisms. We first assessed the effects of LP on Meg-01 megakaryocytic cells regarding proliferation, apoptosis, and differentiation using Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assays, Western blot analysis, and flow cytometry for apoptosis and CD41 expression as a differentiation marker. Following this, LP was administered intraperitoneally at 60 mg/(kg·d) for 11 days to ITP mice. We quantified peripheral blood platelets and bone marrow megakaryocytes, measured spleen and thymus indices, and assessed serum levels of stem cell factor (SCF), interleukin-3 (IL-3), interleukin-6 (IL-6), and platelet factor-4 (PF-4) via enzyme-linked immunosorbent assay (ELISA). Flow cytometry quantified T-helper cells (CD4<sup>+</sup>), cytotoxic T cells (CD8<sup>+</sup>), and regulatory T cells (Tregs). LP significantly induced apoptosis in Meg-01 cells while not markedly affecting differentiation. In ITP mice, LP effectively prevented platelet decline without affecting megakaryocyte counts or maturity. Increased SCF, IL-3, and IL-6 levels, alongside decreased PF-4 levels, correlated with enhanced platelet production. Moreover, CD4<sup>+</sup>/CD8<sup>+</sup> ratios and Treg populations increased, contributing to reduced platelet destruction. In conclusion, LP exerts a protective effect in ITP by modulating SCF, IL-3, IL-6, and PF-4 levels and restoring the balance of T cell subtypes, elucidating its therapeutic potential.</p>\",\"PeriodicalId\":16261,\"journal\":{\"name\":\"Journal of Interferon and Cytokine Research\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2025-03-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Interferon and Cytokine Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1089/jir.2024.0256\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Interferon and Cytokine Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1089/jir.2024.0256","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Lienal Polypeptide Decreases Immune Thrombocytopenia in a Mouse Model by Upregulating Cytokine Production and Increasing the Levels of CD4+, CD8+, and T Regulatory Cells.
Primary immune thrombocytopenia (ITP) is a condition marked by immune-mediated inadequate platelet production or excessive destruction. This study investigates the effects of Lienal polypeptide injection (LP) on T lymphocyte subgroups in the spleen and thymus, megakaryocyte counts in the bone marrow, and cytokine levels related to megakaryocyte development in mice with antibody-induced ITP, aiming to elucidate potential therapeutic mechanisms. We first assessed the effects of LP on Meg-01 megakaryocytic cells regarding proliferation, apoptosis, and differentiation using Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assays, Western blot analysis, and flow cytometry for apoptosis and CD41 expression as a differentiation marker. Following this, LP was administered intraperitoneally at 60 mg/(kg·d) for 11 days to ITP mice. We quantified peripheral blood platelets and bone marrow megakaryocytes, measured spleen and thymus indices, and assessed serum levels of stem cell factor (SCF), interleukin-3 (IL-3), interleukin-6 (IL-6), and platelet factor-4 (PF-4) via enzyme-linked immunosorbent assay (ELISA). Flow cytometry quantified T-helper cells (CD4+), cytotoxic T cells (CD8+), and regulatory T cells (Tregs). LP significantly induced apoptosis in Meg-01 cells while not markedly affecting differentiation. In ITP mice, LP effectively prevented platelet decline without affecting megakaryocyte counts or maturity. Increased SCF, IL-3, and IL-6 levels, alongside decreased PF-4 levels, correlated with enhanced platelet production. Moreover, CD4+/CD8+ ratios and Treg populations increased, contributing to reduced platelet destruction. In conclusion, LP exerts a protective effect in ITP by modulating SCF, IL-3, IL-6, and PF-4 levels and restoring the balance of T cell subtypes, elucidating its therapeutic potential.
期刊介绍:
Journal of Interferon & Cytokine Research (JICR) provides the latest groundbreaking research on all aspects of IFNs and cytokines. The Journal delivers current findings on emerging topics in this niche community, including the role of IFNs in the therapy of diseases such as multiple sclerosis, the understanding of the third class of IFNs, and the identification and function of IFN-inducible genes.