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1.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 40(3): 215-221, 2024 Mar.
Article in Chinese | MEDLINE | ID: mdl-38512031

ABSTRACT

Objective To compare the functional differences between bone marrow derived macrophages and peritoneal macrophages, which may provide the basis for the selection of macrophages in immunological research and immunoregulatory drug evaluation. Methods Marophage colony-stimulating factor (M-CSF) was used to induce the differentiation of bone marrow monocytes into macrophages, and thioglycolate medium was used to induce peritonitis to obtain peritoneal macrophages. After both macrophages being stimulated by zymosan, LPS, R848 and CpG respectively, mRNA levels of tumor necrosis factor α(TNF-α), interleukin 6(IL-6), macrophage inflammatory protein 1α(MIP-1α), monocyte chemoattractant protein 1(MCP-1) were measured by Real-time fluorescent quantitative PCR and the concentrations of secreted TNF-α, IL-6, MIP-1α and MCP-1 were detected by ELISA. In addition, the expression of costimulatory molecules CD80, CD86, CD40 and histocompatibility complex II (MHC II) on the cell surface was analyzed by flow cytometry. Results After inducing by different TLR ligands, mRNA expression levels of inflammatory cytokines and chemokines were increased in both macrophages. The secretion of TNF-α, IL-6, MIP-1α and MCP-1 in peritoneal macrophages and the expression of CD86 and MHC II on the surface of peritoneal macrophages were significantly higher than those of bone marrow derived macrophages. Conclusion There are significant differences in the expression of inflammatory factors, chemokines, costimulatory molecules, and histocompatibility complex between bone marrow derived macrophages and peritoneal macrophages. Peritoneal macrophages have more complete macrophage function and is more suitable for immunological research and immunomodulatory drug evaluation.


Subject(s)
Bone Marrow , Peritoneal Cavity , Animals , Mice , Chemokine CCL3/genetics , Interleukin-6 , Tumor Necrosis Factor-alpha , Macrophages , B7-1 Antigen , CD40 Antigens , RNA, Messenger
2.
Thromb Haemost ; 2024 Feb 09.
Article in English | MEDLINE | ID: mdl-38224965

ABSTRACT

BACKGROUND: Vascular injury results in uncontrollable hemorrhage in hemorrhagic diseases and excessive antithrombotic therapy. Safe and efficient hemostatic agents which can be orally administered are urgently needed. Platelets play indispensable roles in hemostasis, but there is no drug exerting hemostatic effects through enhancing platelet function. METHODS: The regulatory effects of icaritin, a natural compound isolated from Herba Epimedii, on the dense granule release, thromboxane A2 (TxA2) synthesis, α-granule release, activation of integrin αIIbß3, and aggregation of platelets induced by multiple agonists were investigated. The effects of icaritin on tail vein bleeding times of warfarin-treated mice were also evaluated. Furthermore, we investigated the underlying mechanisms by which icaritin exerted its pharmacological effects. RESULTS: Icaritin alone did not activate platelets, but significantly potentiated the dense granule release, α-granule release, activation of integrin αIIbß3, and aggregation of platelets induced by thrombin and U46619. Icaritin also shortened tail vein bleeding times of mice treated with warfarin. In addition, phosphorylated proteome analysis, immunoblotting analysis, and pharmacological research revealed that icaritin sensitized the activation of phospholipase Cγ2 (PLCγ2)-protein kinase C (PKC) signaling pathways, which play important roles in platelet activation. CONCLUSION: Icaritin can sensitize platelet activation induced by thrombin and TxA2 through enhancing the activation of PLCγ2-PKC signaling pathways and promote hemostasis, and has potential to be developed into a novel orally deliverable therapeutic agent for hemorrhages.

3.
Int Immunopharmacol ; 113(Pt B): 109469, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36435062

ABSTRACT

Timely treatment of acute inflammatory reactions induced by fungi or bacteria is essential to prevent infectious damage. Ibrutinib is a Bruton's tyrosine kinase (BTK) inhibitor which is used to treat various lymphoid cancers. It is also known that BTK plays important roles in innate immunity and inflammatory response. In the present study, we investigated the regulatory effects of Ibrutinib on the activation of neutrophils and macrophages and its therapeutic effects on acute peritonitis. In addition, we also studied its anti-inflammatory mechanisms. The results showed that Ibrutinib inhibited the expression and secretion of inflammatory factors in macrophages induced by multiple Toll-like receptor (TLR) agonists. In the study of neutrophils, Ibrutinib selectively suppressed the activation, superoxide release, and calcium influx of neutrophils stimulated by zymosan. Furthermore, in zymosan-induced mice acute peritonitis, Ibrutinib significantly reduced the infiltration of neutrophils into peritoneal cavity, the release of myeloperoxidase (MPO) and ß-glucuronidase as well as the production of inflammatory factors in peritoneal cavity. In mechanism study, Ibrutinib selectively inhibited the phosphorylation of PLCγ2, PKCδ, and ERK1/2 in neutrophils induced by zymosan. Collectively, Ibrutinib can significantly inhibit the activation of neutrophils and macrophages by inhibiting BTK-PLCγ2-PKC signaling pathway, and has great potential to be developed into therapeutic drug for acute inflammatory diseases.


Subject(s)
Neutrophils , Peritonitis , Animals , Mice , Zymosan , Phospholipase C gamma , Macrophages , Adjuvants, Immunologic , Peritonitis/chemically induced , Peritonitis/drug therapy
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