Structure-activity relationships in glucocorticoid-induced apoptosis in T lymphocytes

Perrin-Wolff, Mallory; Bertoglio, Jacques; Bressac, Brigitte; Bohuon, C; Pallardy, Marc

doi:10.1016/0006-2952(94)00527-s

Cited by 18 publications

(7 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2). Similar to the results obtained by Perrin-Wolff et al [1995], there was no appearance of apoptosis by annexin-V FITC analysis, with up to a 12-hr treatment of the solvent (DMSO); apoptosis began to appear at 15 hr of treatment, presumably because the IL-2 concentration became low relative to the increasing number of cells. The concentration of IL-2 was established to allow cell division without affording protection from the occurrence of apoptosis [Singh et al, 1994].…”

Section: Standardization Of In Vitro Micronucleus Test Protocol In Ctsupporting

confidence: 85%

Using CTLL‐2 and CTLL‐2 bcl2 cells to avoid interference by apoptosis in the in vitro micronucleus test

Meintières

Biola

Pallardy

et al. 2003

Environ and Mol Mutagen

View full text Add to dashboard Cite

In vitro assays for chromosome aberrations (i.e., in vitro micronucleus and in vitro metaphase analysis tests) frequently produce false-positive or exaggerated-positive results. Our previous work suggested that apoptosis interferes with these tests, producing misleading results. These previous studies were conducted by performing the in vitro micronucleus test in CTLL-2 cells and a CTLL-2 cell derivative stably transfected with the apoptosis inhibitor gene bcl2. In the present study, these previous observations were extended by examining micronucleus induction with a larger number of compounds in both CTLL-2 and CTLL-2 bcl2 cells and measuring apoptosis with annexin V-FITC. Both cell lines were treated with different classes of compounds that were anticipated to be exclusively apoptosis inducers, or compounds known to be clastogens or aneugens, some of which were anticipated to be both genotoxic and apoptotic. We were able to confirm that compounds that are only apoptogenic induced micronuclei in CTLL-2 but not CTLL-2 bcl2 cells, indicating that the positive responses are due to apoptosis in CTLL-2 cells. Some genotoxins (clastogens and aneugens) did not produce apoptosis by the annexin V assay and gave similar responses in CTLL-2 and CTLL-2 bcl2 cells. Finally, higher responses were induced in CTLL-2 cells compared to CTLL-2 bcl2 cells that were treated with aneugens or clastogens that were also apoptosis inducers, suggesting that the greater response in CTLL-2 cells is a consequence of both genotoxicity and apoptosis. Finally, it was demonstrated that just eliminating CTLL-2 cells having three or more micronuclei from scoring was not adequate for correctly evaluating agents that only produce apoptosis. The results indicate that coupling the in vitro micronucleus test in both CTLL-2 and CTLL-2 bcl2 cells with the measurement of apoptosis is able to distinguish the genotoxic effects of a test compound from its apoptotic potential and is able to avoid interference from apoptosis in the in vitro micronucleus test. These observations may provide the basis for a useful genotoxicity assay.

show abstract

Section: Standardization Of In Vitro Micronucleus Test Protocol In Ctsupporting

confidence: 85%

Using CTLL‐2 and CTLL‐2 bcl2 cells to avoid interference by apoptosis in the in vitro micronucleus test

Meintières

Biola

Pallardy

et al. 2003

Environ and Mol Mutagen

View full text Add to dashboard Cite

show abstract

“…Second, as dexamethasone was used for treatment, the outcome may be different from betamethasone. Structural differences between dexamethasone and betamethasone were shown to affect apoptotic activity (Perrin-Wolff et al, 1995). Finally, mobility of the dexamethasone-exposed rats may have been overall compromised as corroborated by a different study using PN3-6 exposure to dexamethasone (Neal et al, 2004).…”

Section: Technical Considerationsmentioning

confidence: 86%

Prenatal Exposure to Betamethasone Decreases Anxiety in Developing Rats: Hippocampal Neuropeptide Y as a Target Molecule

Velı́šek

2006

Neuropsychopharmacol

View full text Add to dashboard Cite

Repeated antenatal administration of betamethasone is frequently used as a life-saving treatment in obstetrics. However, limited information is available about the outcome of this therapy in children. The initial prospective studies indicate that there are behavioral impairments in children exposed to repeated courses of prenatal betamethasone during the third trimester of pregnancy. In this study, pregnant rats received two betamethasone injections on day 15 of gestation. Using immunohistochemistry, the expression of a powerful anxiolytic molecule neuropeptide Y (NPY) was determined on postnatal day (PN) 20 in the hippocampus and basolateral amygdala (structures related to anxiety and fear) of the offspring. Prenatal betamethasone exposure induced significant increases in NPY expression in the hippocampus but not in the amygdala. Indeed, behavioral tests in the offspring, between PN20 and PN22 in the open field, on the horizontal bar, and in the elevated plus maze, indicated decreases in anxiety, without impairments in motor performance or total activity. Decreased body weight in betamethasone-exposed rats confirmed long-lasting effects of prenatal exposure. Thus, prenatal betamethasone treatment consistently increases hippocampal NPY, with decreases in anxiety-related behaviors and hippocampal role in anxiety in rats. Animal models may assist in differentiation between pathways of the desired main effect of the antenatal corticosteroid treatment and pathways of unwanted side effects. This differentiation can lead to specific therapeutic interventions directed against the side effects without eliminating the beneficial main effect of the corticosteroid treatment.

show abstract

“…For several years, the immunosuppressive effects of GCs have been ascribed to their capacity to inhibit T cell-mediated immunity. Indeed, GCs are known to inhibit the production by T cells of cytokines such as IL-2 [2] and IFN-␥ [3], to inhibit IL-2-driven T cell proliferation [4], and to induce T cell apoptosis [5]. However, the pharmacological effects of GCs are not only a result of the inhibition of T cell functions, and it is now clearly accepted that GCs also affect the function of APCs.…”

Section: Introductionmentioning

confidence: 99%

Glucocorticoids inhibit dendritic cell maturation induced by Toll-like receptor 7 and Toll-like receptor 8

Larangé

Antonios

Pallardy

et al. 2011

Journal of Leukocyte Biology

View full text Add to dashboard Cite

GCs are widely prescribed to treat inflammatory disorders and autoimmune and allergic diseases. Their anti-inflammatory and immunosuppressive effects may be related, in part, to their ability to control the maturation and functions of DCs. Here, we report that GCs inhibit the maturation of human CD34-DCs induced by the TLR7 agonist imiquimod and the TLR8 agonist 3M-002. GCs down-regulate the expression of CD86, CD40, CD83, CCR7, and HLA-DR on DCs and inhibit IL-6 and IL-12p40 production by DCs following TLR7 and TLR8 stimulation. This inhibitory effect is abolished by RU486, suggesting a role for GR transcriptional activity. Our results also show that GCs do not affect TLR-mediated DNA-binding activity of NF-κBp65. We observe that GCs control the activation of JNK induced by TLR agonists, without affecting its upstream MKK4. However, p38MAPK activation is not affected by GCs. Concomitantly to JNK inhibition, we observe the induction of the DUSP MKP-1 but not of other DUSPs by GCs. However, although silencing of MKP-1 in DCs reverses GC-mediated JNK inhibition, no significant effect on GC-induced inhibition of DC maturation was evidenced. Our results show that GCs alter DC maturation in response to TLR7 or TLR8 through a mechanism involving GR transcriptional activity.

show abstract

Structure-activity relationships in glucocorticoid-induced apoptosis in T lymphocytes

Cited by 18 publications

References 26 publications

Using CTLL‐2 and CTLL‐2 bcl2 cells to avoid interference by apoptosis in the in vitro micronucleus test

Using CTLL‐2 and CTLL‐2 bcl2 cells to avoid interference by apoptosis in the in vitro micronucleus test

Prenatal Exposure to Betamethasone Decreases Anxiety in Developing Rats: Hippocampal Neuropeptide Y as a Target Molecule

Glucocorticoids inhibit dendritic cell maturation induced by Toll-like receptor 7 and Toll-like receptor 8

Contact Info

Product

Resources

About