Hyperglycemia is an essential factor leading to micro- and macrovascular diabetic complications. Macrophages are key innate immune regulators of inflammation that undergo 2 major directions of functional polarization: classically (M1) and alternatively (M2) activated macrophages. The aim of the study was to examine the effect of hyperglycemia on transcriptional activation of M0, M1 and M2 human macrophages.
Hyperglycemia induces mixed M1/M2 cytokine profile in primary human monocyte-derived macrophages.
Specimen part, Treatment, Subject
View SamplesThe goal of the study was to identify the effects of TGF-beta on primary human macrophages maturated under different conditions.
Activation of a TGF-beta-specific multistep gene expression program in mature macrophages requires glucocorticoid-mediated surface expression of TGF-beta receptor II.
No sample metadata fields
View SamplesAnalysis of bone marrow derived macrophages (BMDM) incubated with dexamethasone&IL4 (Dexa+IL4), B16F1 tumor conditioned medium (cmB16), and B16F1 tumor conditioned medium supplemented with dexamethasone&IL4 (cmB16+dexa+IL4). Results allow detection of genes that require synergistic stimulation of tumor factors and Th2 cytokines.
Synergistic activation by p38MAPK and glucocorticoid signaling mediates induction of M2-like tumor-associated macrophages expressing the novel CD20 homolog MS4A8A.
Specimen part
View SamplesTranscription factor FoxQ1 belongs to family of Fox transcription factors containing forkhead box (winged helix) domain. This family of proteins plays an important role in cell growth, proliferation, and differentiation. Expression of FoxQ1 was found in cancer cells and was associated with increased migration and invasion. Recently, elevated FoxQ1 expression was found in IL4 stimulated macrophages.
IL-4 driven transcription factor FoxQ1 is expressed by monocytes in atopic dermatitis and stimulates monocyte migration.
Cell line
View SamplesTumor-associated macrophages (TAMs) represent alternatively activated (M2) macrophages that support tumor growth. Previously, we have described a special LYVE-1(+) M2 TAM subset in vitro and in vivo; gene profiling of this TAM subset identified MS4A8A as a novel TAM molecule expressed in vivo by TAM in mammary carcinoma and malignant melanoma. In vitro, Ms4a8a mRNA and MS4A8A protein expression was strongly induced in bone marrow-derived macrophages (BMDMs) by combining M2 mediators (IL-4, glucocorticoids) and tumor-conditioned media (TCM). Admixture of MS4A8A(+) TCM/IL-4/GC-treated BMDM significantly enhanced the tumor growth rate of subcutaneously transplanted TS/A mammary carcinomas. Upon forced overexpression of MS4A8A, Raw 264.7 macrophage-like cells displayed a special gene signature. Admixture of these MS4A8A(+) Raw 264.7 cells also significantly enhanced the tumor growth rate of subcutaneously transplanted mammary carcinomas. To identify the signaling pathways involved in synergistic induction of MS4A8A, the major signaling cascades with known functions in TAM were analyzed. Although inhibitors of NF-B activation and of the MAPK JNK and ERK did not show relevant effects, the p38/ MAPK inhibitor SB203580 strongly and highly significantly (p > 0.001) inhibited MS4A8A expression on mRNA and protein level. In addition, MS4A8A expression was restricted in M2 BMDM from mice with defective GC receptor (GR) dimerization indicating that classical GR gene regulation is mandatory for MS4A8A induction. In conclusion, expression of MS4A8A within the complex signal integration during macrophage immune responses may act to fine tune gene regulation. Furthermore, MS4A8A(+) TAM may serve as a novel cellular target for selective cancer therapy.
Synergistic activation by p38MAPK and glucocorticoid signaling mediates induction of M2-like tumor-associated macrophages expressing the novel CD20 homolog MS4A8A.
Specimen part
View SamplesLymph node vs. tonsil
Differential expression of a gene signature for scavenger/lectin receptors by endothelial cells and macrophages in human lymph node sinuses, the primary sites of regional metastasis.
No sample metadata fields
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