Regulation of Tumor Necrosis Factor-α by Peptide Lv in Bone Marrow Macrophages and Synovium
| Autor: | Manabu Mukai, Kentaro Uchida, Tadashi Okubo, Shotaro Takano, Toshihide Matsumoto, Masashi Satoh, Gen Inoue, Masashi Takaso |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Medicine (General) medicine.medical_treatment Inflammation Peptide macrophage Proinflammatory cytokine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine R5-920 Synovitis medicine Macrophage Original Research 030203 arthritis & rheumatology chemistry.chemical_classification General Medicine medicine.disease peptide Lv Vascular endothelial growth factor 030104 developmental biology Cytokine chemistry Cancer research Medicine Tumor necrosis factor alpha medicine.symptom tumor necrosis factor-α synovitis V-set and transmembrane domain-containing 4 |
| Zdroj: | Frontiers in Medicine, Vol 8 (2021) Frontiers in Medicine |
| Popis: | 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, andTnfa, Il1b, Il6, andIfngexpression 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-inducedTnfaandIfngexpression and TNF-α and IFN-γ production were evaluated in BMM isolated from wild-type andpeptide Lv-deficient mice. Additionally,TnfaandIfngexpression levels were compared between wild-type andpeptide 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 frompeptide Lv-deficient mice compared to wild-type mice. Synovial TNF-α expression in the injured knee was elevated inpeptide 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. |
| Databáze: | OpenAIRE |
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