Interleukin 2 production in B cell chronic lymphocytic leukemia

Interleukin 2 (IL 2) production by phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) was investigated in 22 patients with active untreated B cell chronic lymphocytic leukemia (B- CLL) and in 15 healthy donors. PBMCs from healthy donors demonstrated an IL 2 synthesis of 12.4 +/- 10 U/mL. B-CLL PBMCs produced a significant amount of IL 2 (8 +/- 6.6 U/mL) despite the low percentage of T cells (13% +/- 8%) associated with this disease compared with that found in healthy donors (63% +/- 7.5%). If IL 2 production is expressed as units per milliliter per 10(4) T cells, its level in patients with B- CLL (1.1 U/mL/10(4) T cells) is five times greater than that of the controls (0.19 units). When expressed as units per milliliter per liter of blood, the B-CLL patients produce approximately 12 times as much IL 2 as controls. IL 2 production in normal controls was doubled after irradiation of PBMCs or addition of indomethacin. This increase was not seen with B-CLL PBMCs suggesting that the latter have been devoid of prostaglandin-producing normal IL 2 suppressor cells. By mixing normal or B-CLL T cells with non-T cells we found that T cells from patients with B-CLL stimulated by normal accessory cells produced the same amount of IL 2 as normal T cells. Moreover, B-CLL non-T cells (mainly B leukemic cells) produced no IL 2 themselves but played a much more efficient role in IL 2 production than did non-T cells from healthy donors. This was not due to detectable IL 1 production by these cells. The IL 2 produced by B-CLL PBMCs was partially purified and recovered in a 16,000 mol wt fraction, the same mol wt as IL 2 from normal cells.</jats:p

Interleukin 2 production in B cell chronic lymphocytic leukemia

Abstract Interleukin 2 (IL 2) production by phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) was investigated in 22 patients with active untreated B cell chronic lymphocytic leukemia (B- CLL) and in 15 healthy donors. PBMCs from healthy donors demonstrated an IL 2 synthesis of 12.4 +/- 10 U/mL. B-CLL PBMCs produced a significant amount of IL 2 (8 +/- 6.6 U/mL) despite the low percentage of T cells (13% +/- 8%) associated with this disease compared with that found in healthy donors (63% +/- 7.5%). If IL 2 production is expressed as units per milliliter per 10(4) T cells, its level in patients with B- CLL (1.1 U/mL/10(4) T cells) is five times greater than that of the controls (0.19 units). When expressed as units per milliliter per liter of blood, the B-CLL patients produce approximately 12 times as much IL 2 as controls. IL 2 production in normal controls was doubled after irradiation of PBMCs or addition of indomethacin. This increase was not seen with B-CLL PBMCs suggesting that the latter have been devoid of prostaglandin-producing normal IL 2 suppressor cells. By mixing normal or B-CLL T cells with non-T cells we found that T cells from patients with B-CLL stimulated by normal accessory cells produced the same amount of IL 2 as normal T cells. Moreover, B-CLL non-T cells (mainly B leukemic cells) produced no IL 2 themselves but played a much more efficient role in IL 2 production than did non-T cells from healthy donors. This was not due to detectable IL 1 production by these cells. The IL 2 produced by B-CLL PBMCs was partially purified and recovered in a 16,000 mol wt fraction, the same mol wt as IL 2 from normal cells.</jats:p

Differential effects of macrophage- and granulocyte-macrophage colony-stimulating factors on cytokine gene expression during rat alveolar macrophage differentiation into multinucleated giant cells (MGC): role for IL-6 in type 2 MGC formation.

Abstract Macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage (GM)-CSF stimulate the differentiation of rat alveolar macrophages (AM) into multinucleated giant cells (MGC) with distinct phenotypes (type 1 and type 2 MGC). In the present study, we analyzed the profile of cytokine gene expression induced respectively, by M-CSF and GM-CSF during rat AM differentiation using reverse transcription-PCR. Enhanced mRNA expression for IL-1alpha, TNF-alpha, and TGF-beta1 was observed 3 h after treatment with M-CSF (50 U/ml) or GM-CSF (50 U/ml). In contrast, IL-6 mRNA expression was increased by GM-CSF but not M-CSF. Kinetic analysis indicated that GM-CSF stimulated IL-6 expression early (1.5 h), with maximal effect observed at 24 h and up to 5 days thereafter. Increased mRNA levels for IL-6 were associated with higher IL-6 activity in the culture media of differentiating AM. IL-6 activity was stimulated 3 h after treatment with GM-CSF and increased with time (up to 5 days). Interestingly, addition of exogenous IL-6 (20-100 ng/ml) alone or in combination with GM-CSF to AM cultures increased slightly and selectively the formation of MGC with type 2 phenotype. Conversely, neutralization of endogenous IL-6 during AM differentiation into MGC inhibited significantly (up to 50%) the formation of type 2 MGC. These results suggest a role for IL-6 in the formation of type 2 MGC and provide some insights into the mechanisms of MGC formation and the processes that regulate it positively.</jats:p

Transformation Foci in IDH1-mutated Gliomas Show STAT3 Phosphorylation and Downregulate the Metabolic Enzyme ETNPPL, a Negative Regulator of Glioma Growth

AbstractIDH1-mutated gliomas are slow-growing brain tumours which progress into high-grade gliomas. The early molecular events causing this progression are ill-defined. Previous studies revealed that 20% of these tumours already have transformation foci. These foci offer opportunities to better understand malignant progression. We used immunohistochemistry and high throughput RNA profiling to characterize foci cells. These have higher pSTAT3 staining revealing activation of JAK/STAT signaling. They downregulate RNAs involved in Wnt signaling (DAAM2, SFRP2), EGFR signaling (MLC1), cytoskeleton and cell-cell communication (EZR, GJA1). In addition, foci cells show reduced levels of RNA coding for Ethanolamine-Phosphate Phospho-Lyase (ETNPPL/AGXT2L1), a lipid metabolism enzyme. ETNPPL is involved in the catabolism of phosphoethanolamine implicated in membrane synthesis. We detected ETNPPL protein in glioma cells as well as in astrocytes in the human brain. Its nuclear localization suggests additional roles for this enzyme. ETNPPL expression is inversely correlated to glioma grade and we found no ETNPPL protein in glioblastomas. Overexpression of ETNPPL reduces the growth of glioma stem cells indicating that this enzyme opposes gliomagenesis. Collectively, these results suggest that a combined alteration in membrane lipid metabolism and STAT3 pathway promotes IDH1-mutated glioma malignant progression.</jats:p