Interleukin-1β induces apoptosis in GL15 glioblastoma-derived human cell line

Abstract

Interleukin 1-beta (IL-1beta) induces apoptosis in a glioblastoma-derived human cell line, exhibiting a poorly differentiated astrocytic phenotype. The apoptotic effect was demonstrated by analyzing nuclear morphology, in situ DNA fragmentation, and by ELISA detection of cytoplasmatic nucleosomes. We correlated the degree of differentiation of GL15 cells with the apoptotic response: 1) 4',6-diamidino-2-phenylindole staining, combined with glial fibrillary acidic protein (GFAP) immunofluorescence, showed that the cells with apoptotic nuclei express low levels of GFAP; and 2) at 13 days of subculture, in a more differentiated state, GL15 cells did not respond with apoptosis to IL-1beta. In this cell line, nonrandom chromosome changes and the expression of SV40 early region have been previously shown. The involvement of p42/p44 mitogen-activated protein kinase (MAPK) pathway in the induction of apoptosis by IL-1beta was hypothesized. Previous studies have shown that SV40 small T antigen partially inhibits phosphatase 2A, leading to an enhancement of the steady-state activity of p42/p44 MAPK pathway. PD-098059, specific inhibitor of p42/p44 MAPK pathway, counteracts the apoptotic effect of IL-1beta, whereas SB-203580, specific inhibitor of p38 stress-activated protein kinase (SAPK) pathway, is ineffective. The imbalance between MAPK and SAPK pathways has been proposed as a key factor in determination of cell fate. Our results demonstrate that a further stimulation of p42/p44 MAPK pathway can constitute a death signal in tumor cells in which genomic damage and MAPK pathway control alterations occur.

Expression of galectin-3 in the tumor immune response in colon cancer

“…Cell death occurred, at least partly, by apoptosis as evidenced by Ann V binding assays and PARP cleavage, in accordance with the high level of cytokines contained in CM-LAM known to be proapoptotic to susceptible tumor cells. 32,33 DLD-1 colon adenocarcinoma cells express a high level of gal-3 in both their cytoplasms and nuclei. We found that CM-LAM induces a marked decrease of the expression of gal-3 in DLD-1 cells at both the mRNA and protein levels.…”

Apoptosis in the lungs of pigs infected with porcine reproductive and respiratory syndrome virus and associations with the production of apoptogenic cytokines

“…Using similar in vitro experiments, both cytokines were shown to induce apoptosis in human cells. IL-1b was shown to induce apoptosis in a glioblastoma-derived human cell line when concentrations between 1 and 200 U/mL were used [6]. Similarly, human monocytes/macrophages underwent apoptosis following treatment with 10 ng/mL of IL-10 [33].…”

“…In the seven noninoculated control pigs, the mean number was 5.3 ± 1.8´10 6 . In PRRSV-inoculated 254 G. Labarque et al pigs, the mean numbers were similar to those of non-inoculated pigs until 3 days PI.…”

“…However, the mechanism of apoptosis in the non-infected cell is unknown. It has been demonstrated that cytokines, such as tumour necrosis factoralpha (TNF-a) [18], interferon-alpha (IFN-a) [28], interleukin (IL)-1 [6,11] and interleukin-10 [12,33] can induce apoptosis. A PRRSV infection generally fails to induce substantial amounts of IFN-a [1,30,32].…”

Expression and Modulation of the Intermediate- Conductance Ca²⁺-Activated K⁺ Channel in Glioblastoma GL-15 Cells

“…Electrophysiological evidence for the presence of the IK Ca channel has also been provided for the C6 rat glioma cell line [22,23]. Here we report the expression of the IK Ca channel in the human glioblastoma GL-15 and U-251 cell lines, both exhibiting a poorly differentiated astrocytic phenotype [24][25][26], and show its modulation by the ERK (extracellular signal-regulated kinase) pathway. The ERKs constitute a family of highly conserved and ubiquitously expressed serine/threonine kinases that are critical components of signalling pathways activated downstream to growth factor receptors or G-protein-linked receptors [27].…”