The transcription factor PU.1 mediates enhancer-promoter looping that is required for IL-1β eRNA and mRNA transcription in mouse melanoma and macrophage cell lines.
The Cd contents, expression of melanoma-associated differentiation gene 5 (MDA5) and its downstream signaling molecules (interferon promoter-stimulating factor 1 (IPS-1), transcription factors interferon regulatory factor 3 (IRF3), and nuclear factor kappa-light chain-enhancer of activated B cells (NF-κB)), the content of cytokines (interleukin 1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α) and beta interferon (IFN-β)), protein levels of heat shock proteins (HSPs), levels of malondialdehyde (MDA), activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), and histopathological changes of spleens were detected on the 20th, 40th, and 60th day.
S. mutans induced IL-1β secretion via caspase-1 activation, and S. mutans-induced IL-1β secretion required absent in melanoma (AIM2), NLR family pyrin domain-containing 3 (NLRP3) and NLR family CARD domain-containing 4 (NLRC4) inflammasome activation.
Sporadic melanoma malignancy is correlated with constitutive secretion of IL-1β in transformed melanocytes suggesting the involvement of inflammasome in melanoma.
Th17 cells cultured in IL1β were also highly polyfunctional, expressing high levels of effector molecules and exhibiting superior short-term control of melanoma in mice, despite reduced stem cell-like properties.
Further, vemurafenib reduced the expression of IL-1 protein in melanoma cell lines and most notably in human tumor biopsies from 11 of 12 melanoma patients undergoing inhibitor treatment.
These results indicate that the repression of melanocyte-differentiation genes by IL-1 produced by stromal cells or by tumor cells themselves may represent an additional mechanism of melanoma immune escape.
IL-1 mRNA was highly expressed in more than half of all tested metastatic human tumor specimens including non-small-cell lung carcinoma, colorectal adenocarcinoma, and melanoma tumor samples.
Melanoma differentiation-associated gene-7 (mda-7), also referred to as IL-24, is a novel growth regulatory cytokine that has been shown to regulate the immune system by inducing the expression of inflammatory cytokines, such as TNF, IL-1, and IL-6.
These effects of host-derived IL-1 alpha and IL-1 beta were not restricted to the melanoma model, but were also observed in DA/3 mammary and prostate cancer cell models.
The role of p38 mitogen-activated protein kinase (MAPK) in IL-1-induced growth inhibition was investigated using IL-1-sensitive human melanoma A375-C2-1 cells and IL-1-resistant A375-R8 cells.
All the transfectant cell lines, but not progenitor A375-5 cells, expressed functional type I IL-1 receptors and could produce IL-6 in response to IL-1, suggesting that the unresponsiveness of A375-5melanoma cells is exactly due to an IL-1 receptor deficiency.
Five early genes associated with IL-1 action in the melanoma cells were isolated by differential screening of a cDNA library, which was enriched for sequences representing IL-1 responsive genes (IRGs).
Biological assay with the D10-G4 clone confirmed the presence of IL-1 alpha in the supernatant of melanoma (ME) 10221 and revealed an IL-1 activity in the supernatant of Me 4024/1.
Culture supernatants from ATL cells (ATL-SN) obtained from the peripheral blood constitutively produced an interleukin-1 (IL-1)-like factor in vitro, as shown by the growth inhibition factor (GIF) assay using the A375 melanoma cell line and the lymphocyte activating factor (LAF) assay using C3H/HeJ thymocytes.
Although melanoma cells exert accessory cell function, functional and immunological assays did not detect IL-1 in the spent medium of the melanoma cell lines.