Expression data from monocytes treated with complement factor H
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PROVIDER: PRJNA532421 | ENA |
REPOSITORIES: ENA
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Project description:Monocyte maturation plays an important role in many physiological and patological processes includning cancer. Complement factor H is a complemnt inhibitor but has been shown to also have various cellular functions. We used microarrays to detail the global programme of gene expression underlying maturationn of monocytes upon FH stimulation and identified distinct classes of up-regulated genes during this process.
2019-10-01 | GSE129670 | GEO
Project description:Expression data from recombinant HSP90α (rHSP90α) treated human monocytes
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Project description:Expression data from S100A9 and HMGB1 treated human CD14+ monocytes
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Project description:Expression data from U937 monocytes treated with LysoPPC and FSL-1
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Project description:Tumor cells modulate host immunity by secreting extracellular vesicles (EV) and soluble factors in circulation. Their interactions with myeloid cells could lead to the generation of myeloid-derived suppressor cells (MDSC), which strongly inhibit the anti-tumor function of T and NK cells. We demonstrated previously that EV derived from mouse and human melanoma cells induced such immunosuppressive activity via upregulating the expression of programmed cell death ligand 1 (PD-L1) on myeloid cells that was dependent on the heat-shock protein 90a (HSP90a) in EV and on the toll-like receptor (TLR) on myeloid cells. Here, we investigated whether soluble HSP90α could convert monocytes into immunosuppressive MDSC. CD14+ monocytes were isolated from the peripheral blood of healthy donors, incubated with human rHSP90α alone or in the presence of inhibitors of TLR4 signaling and analyzed by flow cytometry. Inhibition of T cell proliferation assay was applied to assess immunosuppressive function of rHSP90α-treated monocytes. The concentration of HSP90α was measured by ELISA in plasma of advanced melanoma patients and correlated with clinical outcome. We found that the incubation of monocytes with rHSP90α for 16 h resulted in a strong upregulation of PD-L1 expression, whereas ROS and NO production as well as the expression of arginase-1, adenosine producing ectoenzymes CD39 and CD73 remained unchanged. The PD-L1 upregulation can be blocked by anti-TLR4 antibodies and an NF-κB inhibitor. After longer incubation (for 24h), rHSP90α-treated monocytes downregulated HLA-DR expression and acquired an augmented viability and resistance to apoptosis. Moreover, these monocytes were converted into MDSC indicated by their capacity to inhibit T cell proliferation mediated by TLR4 signaling as well as PD-L1 and indolamin-2,3-Dioxygenase (IDO) 1 expression. Higher levels of HSP90α in plasma of melanoma patients correlated with augmented PD-L1 expression on circulating monocytic (M) MDSC. Furthermore, melanoma patients with high levels of HSP90α displayed shorter progression-free survival (PSF) upon the treatment with immune checkpoint inhibitors (ICI).
2022-06-29 | GSE207075 | GEO
Project description:Factor H (FH) is a critical regulator of the alternative complement pathway preventing uncontrolled complement activation. Its role in mitigating complement-mediated injury is evident in diseases such as dense deposit disease and age related macular degeneration characterized by significant macrophage (Mo) infiltration. While primarily synthesized in the liver, FH is also produced by other cells, including monocytes and Mos. However, the influence of FH on these cells remains incompletely understood. This study explores the functions of FH in rodent bone marrow-derived Mos, revealing FH-dependent regulation of genes linked to proliferation and inflammation, including C3aR, the receptor for C3a generated on complement activation. Further, our findings demonstrate that intrinsic FH deficiency in Mos enhances proliferation, trafficking, migration, and reduces phagocytosis. FH-deficient Mos exhibit metabolic alterations characterized by reduced oxidative phosphorylation and glycolysis. Notably, our results show for the first time that FH in Mos influences non-canonical functions through downstream C3a/C3aR signaling, modulating calcium levels and the activity of transient receptor potential cation channel, subfamily M, member 7 (TRPM7). Inhibiting TRPM7 activity with FTY720 reduces Mo proliferation, and blocking C3a/C3aR signaling mitigates TRPM7-related alterations and proliferation in Mos. In summary, this study highlights FH's functional relevance in maintaining homeostasis in Mos, where it modulates functions in a cell-autonomous manner, regulating TRPM7 through C3a/C3aR signaling pathways, offering therapeutic avenues for kidney disease and other inflammatory conditions.
2026-05-05 | GSE279157 | GEO
Project description:Complement Factor H maintains macrophage homeostasis through TRPM7 signaling
| PRJNA1170995 | ENA
Project description:Purpose: The complement system is closely linked to the pathogenesis of age-related macular degeneration (AMD). Several complement genes are expressed in retinal pigment epithelium (RPE), and complement proteins accumulate in drusen. Further, a common variant of complement factor H (CFH) confers increased risk of developing AMD. Because the mechanisms by which changes in the function of CFH influence development of AMD are unclear, we examined ocular complement expression as a consequence of age in control and CFH null mutant mice. Methods: Gene expression in neuroretinas and RPE/choroid from young and aged WT and Cfh-/- C57BL/6J mice was analysed by microarrays. Expression of a wide range of complement genes was compared to expression in splenocytes and in liver tissue by qRT-PCR. Results: An age-associated increased expression of complement, particularly C1q, C3 and Factor B, in the RPE/choroid coincided with increased expression of the negative regulators Cfh and Cd59a in the neuroretina. Young mice deficient in CFH expressed Cd59a similar to WT, but failed to upregulate Cd59a expression with age. Both hepatic and splenic expression of Cd59a increased with age regardless of Cfh genotype. Conclusions: While the connection between CFH deficiency and failure to up-regulate CD59a remains unknown, these results suggest that expression of CD59 is tissue-specific and that neuroretinal regulation depends on CFH. This could contribute to the visual functional deficits and morphological changes in the Cfh-/- mouse retina that occur with age, and further suggests that deficient neuroretinal regulation of complement could represent an early event in AMD. Gene expression in neuroretinas and RPE/choroid from young and aged WT and Cfh-/- mice, 4 biological replicates in each group.
2012-10-02 | E-GEOD-38671 | biostudies-arrayexpress
Project description:Purpose: The complement system is closely linked to the pathogenesis of age-related macular degeneration (AMD). Several complement genes are expressed in retinal pigment epithelium (RPE), and complement proteins accumulate in drusen. Further, a common variant of complement factor H (CFH) confers increased risk of developing AMD. Because the mechanisms by which changes in the function of CFH influence development of AMD are unclear, we examined ocular complement expression as a consequence of age in control and CFH null mutant mice. Methods: Gene expression in neuroretinas and RPE/choroid from young and aged WT and Cfh-/- C57BL/6J mice was analysed by microarrays. Expression of a wide range of complement genes was compared to expression in splenocytes and in liver tissue by qRT-PCR. Results: An age-associated increased expression of complement, particularly C1q, C3 and Factor B, in the RPE/choroid coincided with increased expression of the negative regulators Cfh and Cd59a in the neuroretina. Young mice deficient in CFH expressed Cd59a similar to WT, but failed to upregulate Cd59a expression with age. Both hepatic and splenic expression of Cd59a increased with age regardless of Cfh genotype. Conclusions: While the connection between CFH deficiency and failure to up-regulate CD59a remains unknown, these results suggest that expression of CD59 is tissue-specific and that neuroretinal regulation depends on CFH. This could contribute to the visual functional deficits and morphological changes in the Cfh-/- mouse retina that occur with age, and further suggests that deficient neuroretinal regulation of complement could represent an early event in AMD.
2012-10-02 | GSE38671 | GEO
Project description:Monocytes and monocyte derived macrophages, besides natural killer (NK) cells, are crucial for elimination of senescent cells. There is evidence that TLR2/6 together with the lipid receptor CD36 may be the pattern recognition receptor that are most involved in the sensing of epitopes connected to cellular aging, senescence and severe cellular distress. Additionally, the interplay of these scavenger receptors is required for uptake of TLR2/6 agonist FSL-1. Therefore, we investigated whether lysophospholipids would induce or interfere with (TLR2/6 mediated) gene regulation in U937 monocytes. Cells were or were not pre-treated with lysophospholipids (10µM) for 1 hour and then stimulated with the TLR2/6 ligand (1µg/ml) for 2 hours.
2023-09-01 | GSE157588 | GEO