Last update 01 Nov 2024

GM-CSF x CD80

Last update 01 Nov 2024

Basic Info

Related Targets

GM-CSFCD80

Drugs associated with GM-CSF x CD80

Ad-CD80-TPE-GM

Target

CD80 x GM-CSF

Mechanism

CD80 modulators [+1]

Active Org.-

Originator Org.

The Institute of Radiation Medicine Academy of Military Medical Sciences PLA

Active Indication-

Inactive Indication

Neoplasms

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with GM-CSF x CD80

100 Translational Medicine associated with GM-CSF x CD80

0 Patents (Medical) associated with GM-CSF x CD80

551

Literatures (Medical) associated with GM-CSF x CD80

03 Jul 2024·Inflammatory Bowel Diseases

Tofacitinib Affects M1-like and M2-like Polarization and Tissue Factor Expression in Macrophages of Healthy Donors and IBD Patients

Article

Author: Neurath, Markus F ; Gabel, Michael ; Knauss, Annkathrin ; Lethen, Isabelle ; Lechner-Grimm, Kristina ; Atreya, Raja ; Weigmann, Benno

AbstractBackgroundTofacitinib, as inhibitor of Janus kinases (JAK), interrupts the transmission of numerous pro-inflammatory cytokines involved in the pathogenesis of inflammatory bowel diseases (IBD). Therefore, tofacitinib provides a potent option to treat ulcerative colitis (UC). Besides the anti-inflammatory potential, inhibition of widespread JAKs carries the risk of side effects. Macrophages are involved in the form of different subtypes in inflammation, wound healing, and even coagulation. This study aimed to explore the balanced use of tofacitinib in M1-like as well as M2-like macrophages of healthy donors and patients with IBD.MethodsMonocytes of healthy donors and patients with chronic courses of IBD were obtained from blood samples. Macrophage colony-stimulating factor (M-CSF)-derived macrophages were treated with tofacitinib (1 µM, 5 µM, 10 µM) and polarized with either lipopolysaccharide and interferon (IFN)-γ towards M1-like-phenotype or with interleukin (IL)-4 towards M2-like-phenotype. ELISA and flow cytometry were used to evaluate cytokine levels and surface molecules.ResultsTofacitinib had a modulating effect on M1-like macrophages whereby the effect on pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-12, IL-23) was less pronounced than the induction of anti-inflammatory IL-10. However, during M2-like polarization tofacitinib impaired the development of the corresponding phenotype becoming evident through decreased IL-10 levels and CD206 expression in treated macrophages. In both phenotypes, tofacitinib strongly downregulated the expression of immunostimulatory molecules (CD80, CD86, CD83, CD40). Furthermore, a dose-dependent correlation between treatment with tofacitinib and expressed tissue factor was noticed.ConclusionsTofacitinib influences both polarizations (M1/M2) and the expression of tissue factor in a dose-dependent manner.

01 Apr 2024·Probiotics and Antimicrobial Proteins

The Effect of Akkermansia muciniphila and Its Outer Membrane Vesicles on MicroRNAs Expression of Inflammatory and Anti-inflammatory Pathways in Human Dendritic Cells

Article

Author: Davar Siadat, Seyed ; Fateh, Abolfazl ; Mofrad, Laya Zoghi ; Asbi, Dariush Norouzian Sham ; Sotoodehnejadnematalahi, Fattah

Probiotics play a crucial role in immunomodulation by regulating dendritic cell (DC) maturation and inducing tolerogenic DCs. Akkermansia muciniphila affects inflammatory response by elevating inhibitory cytokines. We aimed to evaluate whether Akkermansia muciniphila and its outer membrane vesicles (OMVs) affect microRNA-155, microRNA-146a, microRNA-34a, and let-7i expression of inflammatory and anti-inflammatory pathways. Peripheral blood mononuclear cells (PBMCs) were isolated from the healthy volunteers. To produce DCs, monocytes were cultivated with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). DCs were allocated into six subgroups: DC + Lipopolysaccharide (LPS), DC + dexamethasone, DC + A. muciniphila (MOI 100, 50), DC + OMVs (50 µg/ml), and DC + PBS. The surface expression of human leukocyte antigen-antigen D related (HLA-DR), CD86, CD80, CD83, CD11c, and CD14 was examined using flow cytometry, and the expression of microRNAs was assessed using qRT-PCR, and the levels of IL-12 and IL-10 were measured using ELISA. A. muciniphila (MOIs 50, 100) could significantly decrease IL-12 levels relative to the LPS group. The IL-10 levels were decreased in the DC + LPS group than the DC + dexamethasone group. Treatment with A. muciniphila (MOI 100) and OMVs could elevate the concentrations of IL-10. DC treatment with LPS led to a significant increment in the expression of microRNA-155, microRNA-34a, and microRNA-146a. The expression of these microRNAs was reversed by A. muciniphilia and its OMVs treatment. Let-7i increased in treatment groups compared to the DC + LPS group. A. muciniphilia (MOI 50) had a substantial effect on the expression of HLA-DR, CD80, and CD83 on DCs. Therefore, DCs treatment with A. muciniphila led to induce tolerogenic DCs and the production of anti-inflammatory IL-10.

01 Mar 2024·Life Sciences

TPX2 influences the regulation of macrophage polarization via the NF-κB pathway in lung adenocarcinoma

Article

Author: Li, Yulin ; Li, Lisha ; Wang, Lina ; Zhang, Haiying

BACKGROUNDLung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer. Xklp2 targeting protein (TPX2), a crucial oncogene exhibits high expression levels in various cancers including LUAD, may serve as a potential target for clinical intervention. Additionally, the growth of lung cancer is significantly influenced by the tumor microenvironment (TME). However, there have been no reports on experiments investigating TPX2 in tumor-infiltrating immune cells (TIICs) in LUAD. Therefore, we verified the effect of TPX2 on macrophage polarization both in vitro and in vivo.METHODSWe silenced TPX2 the gene in A549 cells and collected supernatants for macrophage culture. We then used flow cytometry and Western blot analysis to assess macrophage polarization. Additionally, we verified the expression of macrophage colony-stimulating factor (M-CSF), and CD163 by immunohistochemistry (IHC) in tissue specimens from LUAD patients. Finally, pathways related to TPX2's regulatory function in macrophage polarization were analyzed through whole genome sequencing, Western blotting, and immunofluorescence (IF).RESULTSSilencing TPX2 can affect the ratio of CD80⁺ M1/CD163⁺ M2 and reduce the polarization of M0 macrophages to CD163⁺ M2 macrophages mainly by inhibiting the expression of M-CSF. In human LUAD tissues, the expression levels of TPX2, M-CSF and CD163 increased with the degree of differentiation. Silencing TPX2 inhibits the NF-κB signaling pathway, thereby reducing the expression of M-CSF, and affecting macrophage polarization.CONCLUSIONSilencing TPX2 can inhibit the expression of M-CSF by blocking the NF-κB signal, thereby reducing CD163⁺ M2 macrophage polarization. The TPX2/NF-κB/M-CSF signaling axis may be involved in regulating macrophage polarization.

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