Suppression of lymphocyte mitogenesis by tamoxifen

Baral, Edward; Kwok, Siuchan; Berczi, István

doi:10.1016/0162-3109(89)90030-1

Cited by 22 publications

(6 citation statements)

References 17 publications

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“…More recently, it was established that TX inhibited significantly the response of rat spleen cells to phytohemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM), and lipid A (LA) in a dose-dependent manner. Estradiol did not have a consistent effect on lymphocyte mitogenesis under the same conditions and did not modify the suppressive effect of TX even when the lymphocytes were treated first with estradiol followed by TX [9]. Similar observations were made in the mixed lymphocyte reaction [10].…”

Section: Introductionsupporting

confidence: 70%

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Suppression of Lymphocyte Mitogenesis by Tamoxifen: Studies on Protein Kinase C, Calmodulin and Calcium

Baral

Nagy²,

Kwok³

et al. 2000

Neuroimmunomodulation

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The effect of tamoxifen (TX; 1.0 μM) on the mitogenic response of rat lymphocytes was compared with the effect of drugs that are known to act on protein kinase C (PKC), calmodulin (CM), and calcium (Ca²⁺). The calcium ionophore A23187 (0.2 μM) was mitogenic on its own which was not influenced by TX. The agents modulating PKC or CM (phorbol-myristate-13-acetate; R24571, chlorpromazine) influenced mitogenesis differently than did TX. General inhibition of lymphocyte proliferation was seen with the Ca²⁺ antagonist agents (EGTA, TMB-8) as with TX. The antiproliferative effect of TX was partially reversed by the increase of Ca²⁺ in the culture medium when T cell mitogens were used, but not in the case of lipid A, a B lymphocyte mitogen. However, the concanavalin A-induced Ca²⁺ influx was further elevated by TX which differed from the effect of the Ca²⁺ channel-blocking agent verapamil. The results suggest that TX resets the threshold stimulus necessary for mitogenesis and is completely reversible.

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Section: Introductionsupporting

confidence: 70%

“…Tissue Culture Conditions Spleen cell cultures were set up in sextuplicate in RPMI-1640 medium containing 2.5% autologous serum as described [9]. For the growth of the prolactin-dependent Nb2 rat thymic lymphoma, Fisher's medium was used with 10% horse serum (HS) and 10% FCS as described by Tanaka et al [23].…”

Section: Preparation Of Spleen Cellsmentioning

confidence: 99%

Suppression of Lymphocyte Mitogenesis by Tamoxifen: Studies on Protein Kinase C, Calmodulin and Calcium

Baral

Nagy²,

Kwok³

et al. 2000

Neuroimmunomodulation

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“…35 Tamoxifen has displayed significant suppression of lymphocyte mitogenesis in the rat spleen in a dose-dependent manner. 36 According to the current study, sigmoidal inhibition of human T lymphocytes in whole blood is observed with an estimated IC 50 of 18 µM. This IC 50 is at a level 10 4 times greater than that expected to be observed clinically from a 10mg dose.…”

Section: Discussionmentioning

confidence: 45%

“…The exact mechanism by which tamoxifen inhibits T cell mitogenesis is unclear but possibly occurs by increasing the threshold stimulus necessary for mitogenesis by an increase in intracellular Ca ++ influx 35 . Tamoxifen has displayed significant suppression of lymphocyte mitogenesis in the rat spleen in a dose‐dependent manner 36 . According to the current study, sigmoidal inhibition of human T lymphocytes in whole blood is observed with an estimated IC 50 of 18 μM.…”

Section: Discussionmentioning

confidence: 55%

Interactions of Prednisolone and Other Immunosuppressants Used in Dual Treatment of Systemic Lupus Erythematosus in Lymphocyte Proliferation Assays

Kamal

Jusko

2004

The Journal of Clinical Pharma

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Systemic lupus erythematosus is an autoimmune disease primarily affecting women. Currently, systemic lupus erythematosus therapy is suboptimal due to adverse effects of immunosuppressants, particularly corticosteroids. This study determines the single effects of prednisolone, dehydroepiandrosterone, bromocriptine, tamoxifen, mycophenolic acid, 2-chloro-2'-deoxyadenosine, azathioprine, and chloroquine on lectin-stimulated proliferation of human T lymphocytes, as well as determining whether there are interactions in the joint effects of prednisolone and these agents. The T lymphocytes from the whole blood of 10 middle-aged women were stimulated by phytohemagglutinin and cultured with varying drug concentrations. The Hill function was used to evaluate single-drug response data. Isobolograms were constructed to qualitatively analyze interactions. Parametric analysis based on competitive and noncompetitive interaction models was further applied to quantify the joint interactions and predict steroid-sparing potential. The surface interaction parameter (psi) estimated from parametric analysis was in concordance with isobolographic inspection for all interactions studied. All interactions favored the noncompetitive model. Results suggest that dehydroepiandrosterone is additive in its effect with prednisolone, whereas tamoxifen interacts synergistically, both providing steroid-sparing effects. Novel immuno-suppressants such as mycophenolic acid may still provide added pharmacologic benefit during therapy despite a slight antagonistic interaction with prednisolone. These studies help rationalize actual or potential use of other drugs with prednisolone in the treatment of systemic lupus erythematosus.

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“…We observed earlier that TX is capable of suppressing humoral and cell-mediated immune reactions in rats (Nagy and Berczi, 1986). T X also suppressed the proliferation of rat lymphocytes in vitro in response to mitogens or in mixed lymphocyte cultures (Baral et al, 1989(Baral et al, , 1991. On the other hand, it was observed that treatment with T X in vitro potentiated the lysis of tumor cells by autologous killer cells from some cancer patients (Baral and Vanky, 1987).…”

Section: Iakmentioning

confidence: 99%

Anti-estrogens enhance the therapeutic effect of lymphokine-activated killer cells on the P815 murine mastocytoma

et al. 1996

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Hellstrom and Hellstrom, 1993).We have observed previously that the treatment of the P815 murine mastocytoma cells with either tamoxifen (TX) or estradiol greatly enhanced the sensitivity of these cells to lysis by LAK cells generated from rat spleen. The cytotoxic potential of LAK cells was not modified consistently by TX and estradiol. When TX-treated target and effector cells were combined, enhanced cytotoxicity characteristic of sensitized target cells, was observed. Treatment with estradiol led to inconsistent results in similar experiments. LAK cell-induced cytotoxicity triggered the breakdown of DNA in P815 targets, which was accelerated by pretreatment with TX. Therefore, TX exerts a priming effect on P815 cells for killer cell-induced apoptotic death (Baral et al., 1994a. We now present experiments indicating that TX and toremifene (TO) are both capable of potentiating the immunotherapy of the P815 mastocytoma in syngeneic DBA2/J mice with LAK cells.

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Suppression of lymphocyte mitogenesis by tamoxifen

Cited by 22 publications

References 17 publications

Suppression of Lymphocyte Mitogenesis by Tamoxifen: Studies on Protein Kinase C, Calmodulin and Calcium

Suppression of Lymphocyte Mitogenesis by Tamoxifen: Studies on Protein Kinase C, Calmodulin and Calcium

Interactions of Prednisolone and Other Immunosuppressants Used in Dual Treatment of Systemic Lupus Erythematosus in Lymphocyte Proliferation Assays

Anti-estrogens enhance the therapeutic effect of lymphokine-activated killer cells on the P815 murine mastocytoma

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