Cytokine mediated apoptosis of granulocyte eosinophils in expressed blood eosiniphilia

Litvinova, L. S.; Ryazantseva, N. V.; Новицкий, В. В.; Григорьева, Е. С.

doi:10.1134/s1990519x08010057

Cited by 5 publications

(4 citation statements)

References 6 publications

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“…Moreover, we previously showed that binding of STAT5 and AP 1 proteins activated by IL-2 to glucocorticoid receptor prevents the formation of complexes of these receptors with cofactors CBP/ p300 or SRC-1a, which blocks the transduction of the proapoptotic signal [3] Mitochondrial factors (cytochrome C, AIF, calcium ions, Apaf-1, etc.) also can mediate the effect of cytokines on programmed cell death [8]. Using fl uorescent indicator of mitochondrial membrane integrity JC-1 we detected a signifi cant increase in the relative content of lymphocytes with reduced mitochondrial transmembrane potential during their incubation with recombinant human IL-2 to 7.61% (6.73-9.29%) compared to 3.70% (3.61-3.74%) in intact culture (p<0.05).…”

Section: Resultsmentioning

confidence: 93%

“…During stress exposure, Bcl-2 and Bcl-X L are located in mitochondrial membranes and close the channels, thus preventing the release of proapoptotic factors from the intermembrane space [8]. A possible mechanism of this process is heterodimerization of Bcl-2 with proapoptotic protein Bax, which leads to blockade of its channel-forming capacity [1].…”

Section: Resultsmentioning

confidence: 99%

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Molecular Mechanisms of the Effect of Interleukin-2 on Apoptosis of Blood Lymphocytes

et al. 2010

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The effects of recombinant IL-2 on apoptosis of lymphocytes of healthy donors were studied in in vitro experiments. It was shown that the inductive and inhibitory effects of IL-2 on apoptotic process depend on the dose of the cytokine and cell microenvironmental conditions. Culturing of lymphocytes with recombinant IL-2 increases the percent of cells with reduced transmembrane potential, reduces the content of intracellular proteins Bcl-2, Bcl-X(L) and и Bax, and increases the level of Bad. The proapoptotic effect of this cytokine is realized with participation of nuclear transcription factor NF-κB and transcription factor P53.

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Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Molecular Mechanisms of the Effect of Interleukin-2 on Apoptosis of Blood Lymphocytes

et al. 2010

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“…Apoptosis and inflammation are the common reactions to lipotoxicity in cells (Weinberg, 2006), and the analysis of canonical pathways and upstream regulators supports this observation. GM-CSF is known to be involved in antiapoptotic processes and macrophage responses to inflammation induced by NEFA (Bahramian et al, 2004;Litvinova et al, 2008). Thus, its presence proves that the elevated level of NEFAs also affects porcine blastocysts via inflammation and apoptosis.…”

Section: Analysis Of Dna Methylation Datamentioning

confidence: 99%

Effects of NEFAs during IVM on pig embryos from granulosa cell‐cocultured oocytes

Shi

Sirard

2021

Molecular Reproduction Devel

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Circulating levels of nonesterified fatty acids (NEFAs) are elevated in some females, which can impair oocyte maturation and embryo development, and may alter the phenotype of the progeny. However, the effects of NEFAs on human embryo development are not clear due to ethical limitations. Thus, we used pig as the model to investigate the impacts of NEFAs on oocyte and embryo due to their similar reproductive and metabolic physiologies to humans. In this study, porcine cumulusoocyte complexes were in vitro maturated under a pathologically high concentration of NEFAs (468 μM palmitic acid, 194 μM stearic acid, and 534 μM oleic acid) with the presence of granulosa cell monolayer, in contrast to control without NEFAs. The mature oocytes were fertilized to produce embryos for further analysis of the transcriptome and DNA methylation patterns. The elevated level of NEFAs decreased the blastocyst rate and delayed the blastocyst development. Ingenuity pathway analysis showed that the most affected gene pathways were related mainly to cell activities, metabolism, and inflammation. These findings indicated that oocytes exposed to the exogenous high level of NEFAs during in vitro maturation resulted in altered gene expression and DNA methylation of early embryos, which have detrimental impacts on blastocyst quality.

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“…Deregulated cell death is a critical finding in patient with hypereosinophilia (Litvinova et al 2008 ). Evading apoptosis is one of the hallmarks of cancer (Hanahan and Weinberg 2011 ) and targeting cell death resistance is a promising therapeutic strategy (Jilg et al 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Comprehensive characterization of central BCL-2 family members in aberrant eosinophils and their impact on therapeutic strategies

Odinius

Buschhorn

Wagner

et al. 2021

J Cancer Res Clin Oncol

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Purpose Hypereosinophilia represents a heterogenous group of severe medical conditions characterized by elevated numbers of eosinophil granulocytes in peripheral blood, bone marrow or tissue. Treatment options for hypereosinophilia remain limited despite recent approaches including IL-5-targeted monoclonal antibodies and tyrosine kinase inhibitors. Methods To understand aberrant survival patterns and options for pharmacologic intervention, we characterized BCL-2-regulated apoptosis signaling by testing for BCL-2 family expression levels as well as pharmacologic inhibition using primary patient samples from diverse subtypes of hypereosinophilia (hypereosinophilic syndrome n = 18, chronic eosinophilic leukemia not otherwise specified n = 9, lymphocyte-variant hypereosinophilia n = 2, myeloproliferative neoplasm with eosinophilia n = 2, eosinophilic granulomatosis with polyangiitis n = 11, reactive eosinophilia n = 3). Results Contrary to published literature, we found no difference in the levels of the lncRNA Morrbid and its target BIM. Yet, we identified a near complete loss of expression of pro-apoptotic PUMA as well as a reduction in anti-apoptotic BCL-2. Accordingly, BCL-2 inhibition using venetoclax failed to achieve cell death induction in eosinophil granulocytes and bone marrow mononuclear cells from patients with hypereosinophilia. In contrast, MCL1 inhibition using S63845 specifically decreased the viability of bone marrow progenitor cells in patients with hypereosinophilia. In patients diagnosed with Chronic Eosinophilic Leukemia (CEL-NOS) or Myeloid and Lymphatic Neoplasia with hypereosinophilia (MLN-Eo) repression of survival was specifically powerful. Conclusion Our study shows that MCL1 inhibition might be a promising therapeutic option for hypereosinophilia patients specifically for CEL-NOS and MLN-Eo.

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Cytokine mediated apoptosis of granulocyte eosinophils in expressed blood eosiniphilia

Cited by 5 publications

References 6 publications

Molecular Mechanisms of the Effect of Interleukin-2 on Apoptosis of Blood Lymphocytes

Molecular Mechanisms of the Effect of Interleukin-2 on Apoptosis of Blood Lymphocytes

Effects of NEFAs during IVM on pig embryos from granulosa cell‐cocultured oocytes

Comprehensive characterization of central BCL-2 family members in aberrant eosinophils and their impact on therapeutic strategies

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