Recombinant hirudin and PAR-1 regulate macrophage polarisation status in diffuse large B-cell lymphoma

被引：1
作者：
Pei, Qiang [1 ,2 ,3 ]
Li, Zihui [1 ,2 ,4 ]
Zhao, Jingjing [1 ,2 ,4 ]
Zhang, Haixi [1 ,2 ,3 ]
Qin, Tao [1 ,2 ,3 ]
Zhao, Juan [1 ,2 ,3 ]
机构：
[1] First Peoples Hosp Yunnan Prov, Dept Hematol, 157 Jinbi St, Kunming 650032, Yunnan, Peoples R China
[2] Kunming Univ Sci & Technol, Affiliated Hosp, Kunming 650032, Yunnan, Peoples R China
[3] Yunnan Prov Clin Ctr Hematol Dis, Kunming, Yunnan, Peoples R China
[4] Kunming Univ Sci & Technol, Med Sch, Kunming 650500, Yunnan, Peoples R China
来源：
BMC BIOTECHNOLOGY | 2024年 / 24卷 / 01期
关键词：
Diffuse large B-cell lymphoma; Macrophage polarisation; Recombinant hirudin; PAR-1; TUMOR-ASSOCIATED MACROPHAGES; PROTEASE-ACTIVATED RECEPTOR-1; KAPPA-B; THROMBIN RECEPTOR; METASTASIS; INVASION; GROWTH; MICROENVIRONMENT; EXPRESSION; MIGRATION;
D O I：
10.1186/s12896-024-00879-w
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
BackgroundDiffuse large B-cell lymphoma (DLBCL) is a malignant tumour. Although some standard therapies have been established to improve the cure rate, they remain ineffective for specific individuals. Therefore, it is meaningful to find more novel therapeutic approaches. Macrophage polarisation is extensively involved in the process of tumour development. Recombinant hirudin (rH) affects macrophages and has been researched frequently in clinical trials lately. Our article validated the regulatory role of rH in macrophage polarisation and the mechanism of PAR-1 by collecting clinical samples and subsequently establishing a cellular model to provide a scientifically supported perspective for discovering new therapeutic approaches.MethodWe assessed the expression of macrophage polarisation markers, cytokines and PAR-1 in clinical samples. We established a cell model by co-culture with THP-1 and OCI-Ly10 cell. We determined the degree of cell polarisation and expression of validation cytokines by flow cytometry, ELISA, and RT-qPCR to confirm the success of the cell model. Subsequently, different doses of rH were added to discover the function of rH on cell polarisation. We confirmed the mechanism of PAR-1 in macrophage polarisation by transfecting si-PAR-1 and pcDNA3.1-PAR-1.ResultsWe found higher expression of M2 macrophage markers (CD163 + CMAF+) and PAR-1 in 32 DLBCL samples. After inducing monocyte differentiation into M0 macrophages and co-culturing with OCI-Ly10 lymphoma cells, we found a trend of these expressions in the cell model consistent with the clinical samples. Subsequently, we discovered that rH promotes the polarisation of M1 macrophages but inhibits the polarisation of M2 macrophages. We also found that PAR-1 regulates macrophage polarisation, inhibiting cell proliferation, migration, invasion and angiogenic capacity.ConclusionrH inhibits macrophage polarisation towards the M2 type and PAR-1 regulates polarisation, proliferation, migration, invasion, and angiogenesis of DLBCL-associated macrophages.
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页数：14
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