Regulation of Tumor Necrosis Factor-α by Peptide Lv in Bone Marrow Macrophages and Synovium

Frontiers in Medicine

article

Manabu Mukai¹  Kentaro Uchida²  Tadashi Okubo³  Shotaro Takano¹  Toshihide Matsumoto⁴  Masashi Satoh⁵  Gen Inoue¹  Masashi Takaso¹ 

[1] Department of Orthopaedic Surgery, Kitasato University School of Medicine;Shonan University of Medical Sciences Research Institute;Department of Laboratory Animal Science, Kitasato University School of Medicine;Department of Pathology, Kitasato University School of Medicine;Department of Immunology, Kitasato University School of Medicine

关键词: V-set and transmembrane domain-containing 4;    peptide Lv;    tumor necrosis factor-α;    macrophage;    synovitis;   

DOI  :  10.3389/fmed.2021.702126

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Background: Bone marrow-derived monocytes/macrophages are recruited into synovial tissue, where they contribute to synovial inflammation in osteoarthritis through inflammatory cytokine production. Recent studies have suggested that V-Set and transmembrane domain-containing 4 (VSTM4) and its fragment, peptide Lv, exhibit immunosuppressive activity on T cells and vascular endothelial growth factor (VEGF)-like activity, respectively. Given that evidence suggests that VEGF may play a role in macrophage function, we investigated peptide Lv-mediated regulation of inflammatory cytokines in bone marrow macrophages (BMMs) and synovial inflammation. Method: To investigate the effects of peptide Lv, BMMs were stimulated with vehicle, LPS, or LPS + peptide Lv, and Tnfa, Il1b, Il6 , and Ifng expression were evaluated using quantitative PCR (qPCR). TNF-α and IFN-γ production was measured using ELISA. To examine the effect of peptide Lv deficiency on macrophages and synovitis, peptide Lv -deficient mice were generated using genome editing. LPS-induced Tnfa and Ifng expression and TNF-α and IFN-γ production were evaluated in BMM isolated from wild-type and peptide Lv -deficient mice. Additionally, Tnfa and Ifng expression levels were compared between wild-type and peptide Lv -deficient mice before and after knee injury. Results: Peptide Lv suppressed the LPS-mediated elevation in TNF-α and IFN-γ. LPS stimulation significantly increased TNF-α and IFN-γ production in BMM derived from peptide Lv -deficient mice compared to wild-type mice. Synovial TNF-α expression in the injured knee was elevated in peptide Lv -deficient compared to wild-type mice. Conclusion: Peptide Lv suppressed TNF-α in macrophages and plays a role in synovial inflammation. Thus, peptide Lv may be a useful therapeutic target for synovitis.

【 授权许可】

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