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Immunology, 2019. 158(3), 206-218, DOI: https://doi.org/10.1111/imm.13102
The role of CCR1 and therapeutic effects of anti-CCL3 antibody in herpes simplex virus-induced Behc et’s disease mouse model
Sayeed HM, Lee ES;Byun HO;Sohn S
Behc et’s disease (BD) is a chronic systemic inflammatory disease with unclear etiopathogenesis. Although gene variants of CC chemokine receptor type 1 (CCR1) have been reported, the protein expression of CCR1 in patients with BD remains unclear. The objective of this study was to analyze the frequencies of CCR1+ cells in a herpes simplex virus-induced mouse model of BD. The frequencies of CCR1+ cells on the surface and in the cytoplasm of peripheral blood mononuclear cells and lymph nodes were analyzed by flow cytometry. The CCR1+ cells were significantly down-regulated in BD mice compared with the normal control and symptom-free control mice. Colchicine and pentoxifylline treatment improved the symptoms of BD and increased the frequencies of CCR1+ cells in BD mice. Treatment with chemokine CC motif ligand 3 (CCL3), a ligand of CCR1, caused BD symptoms to deteriorate in 10 of 16 BD mice (62 5%) via down-regulation of CCR1+ cells. Anti-CCL3 antibody treatment ameliorated BD symptoms in 10 of 20 mice (50%) and significantly decreased the disease severity score compared with CCL3-treated BD mice(P = 0 01) via up-regulation of CCR1+ cell frequencies. In patients with BD, plasma levels of CCL3 in an active state were significantly higher than in healthy control individuals (P = 0 02). These results show that the upregulation of CCR1+ cells was related to the control of systemic inflammation of BD in mouse models.
- DOI: https://doi.org/10.1111/imm.13102
- ISBN or ISSN: 1365-2567
- 본 연구는 질병관리본부 연구개발과제연구비를 지원받아 수행되었습니다.
- This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.