Recombinant hirudin and PAR-1 regulate macrophage polarisation status in diffuse large B-cell lymphoma.
Diffuse large B-cell lymphoma
Macrophage polarisation
PAR-1
Recombinant hirudin
Journal
BMC biotechnology
ISSN: 1472-6750
Titre abrégé: BMC Biotechnol
Pays: England
ID NLM: 101088663
Informations de publication
Date de publication:
12 Aug 2024
12 Aug 2024
Historique:
received:
20
01
2024
accepted:
22
07
2024
medline:
13
8
2024
pubmed:
13
8
2024
entrez:
12
8
2024
Statut:
epublish
Résumé
Diffuse 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. We 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. We 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. rH inhibits macrophage polarisation towards the M2 type and PAR-1 regulates polarisation, proliferation, migration, invasion, and angiogenesis of DLBCL-associated macrophages.
Sections du résumé
BACKGROUND
BACKGROUND
Diffuse 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.
METHOD
METHODS
We 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.
RESULTS
RESULTS
We 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.
CONCLUSION
CONCLUSIONS
rH inhibits macrophage polarisation towards the M2 type and PAR-1 regulates polarisation, proliferation, migration, invasion, and angiogenesis of DLBCL-associated macrophages.
Identifiants
pubmed: 39135175
doi: 10.1186/s12896-024-00879-w
pii: 10.1186/s12896-024-00879-w
doi:
Substances chimiques
Receptor, PAR-1
0
Hirudins
0
Recombinant Proteins
0
Cytokines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
55Subventions
Organisme : The Joint Special Program of Yunnan Province Department and Kunming Medical University for applied basic research
ID : No.201901C070074
Organisme : The Joint Special Program of Yunnan Province Department and Kunming Medical University for applied basic research
ID : No.201901C070074
Organisme : The Joint Special Program of Yunnan Province Department and Kunming Medical University for applied basic research
ID : No.201901C070074
Organisme : The Joint Special Program of Yunnan Province Department and Kunming Medical University for applied basic research
ID : No.201901C070074
Organisme : The Joint Special Program of Yunnan Province Department and Kunming Medical University for applied basic research
ID : No.201901C070074
Organisme : The Joint Special Program of Yunnan Province Department and Kunming Medical University for applied basic research
ID : No.201901C070074
Organisme : The Open project of Yunnan Province Clinical Center for Hematologic Disease
ID : No. 2019LCZXKF-XY10
Organisme : The Open project of Yunnan Province Clinical Center for Hematologic Disease
ID : No. 2019LCZXKF-XY10
Organisme : The Open project of Yunnan Province Clinical Center for Hematologic Disease
ID : No. 2019LCZXKF-XY10
Organisme : The Open project of Yunnan Province Clinical Center for Hematologic Disease
ID : No. 2019LCZXKF-XY10
Organisme : The Open project of Yunnan Province Clinical Center for Hematologic Disease
ID : No. 2019LCZXKF-XY10
Organisme : The Open project of Yunnan Province Clinical Center for Hematologic Disease
ID : No. 2019LCZXKF-XY10
Informations de copyright
© 2024. The Author(s).
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