CD69 expression induced by thapsigargin, phorbol ester and ouabain on thymocytes is dependent on external Ca2+ entry

Mascarenhas, Sandra Rodrigues; Echevarria-Lima, Juliana; Santos, Neusa; Rumjanek, Vivian M.

doi:10.1016/s0024-3205(03)00377-1

Cited by 26 publications

(21 citation statements)

References 39 publications

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“…However, the pathways regulating the expression of CD69 are different depending on the cell type (Vazquez et al 2009). It is not entirely clear what cellular signals contribute to CD69 induction in CD8 + T cells, but it is known that Ca 2+ influx into T cells increases CD69 expression (Testi et al 1994) and, at least in thymocytes, extracellular Ca 2+ was found to be critical for CD69 induction (Rodrigues Mascarenhas et al 2003). In these studies Δ 9 -THC synergized with Io to increase CD69 expression suggesting that Ca 2+ plays an important role in the Δ 9 -THC-mediated increase of CD69 expression.…”

Section: Discussionmentioning

confidence: 99%

Δ9-Tetrahydrocannabinol Suppresses Cytotoxic T Lymphocyte Function Independent of CB1 and CB2, Disrupting Early Activation Events

Karmaus¹,

Chen²,

Kaplan

et al. 2011

J Neuroimmune Pharmacol

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Previously, CD8+ T cells were found to be a sensitive target for suppression by Δ9-tetrahydrocannabinol (Δ9-THC) in a murine model of influenza infection. To study the effect of Δ9-THC on CD8+ cytotoxic T lymphocytes (CTL), an allogeneic model of MHC I mismatch was used to elicit CTL. In addition, to determine the requirement for the cannabinoid receptors 1 (CB1) and 2 (CB2) in Δ9-THC-mediated CTL response modulation, mice null for both receptors were used (CB1 −/−CB2 −/−). Δ9-THC suppressed CTL function independent of CB1 and CB2 as evidenced by reduction of 51Cr release by CTL generated from CB1 −/−CB2 −/− mice. Furthermore, viability in CD4+ and CD8+ cells was reduced in a concentration-dependent manner with Δ9-THC, independent of CB1 and CB2, but no effect of Δ9-THC on proliferation was observed, suggesting that Δ9-THC decreases the number of T cells initially activated. Δ9-THC increased expression of the activation markers, CD69 in CD8+ cells and CD25 in CD4+ cells in a concentration-dependent manner in cells derived from WT and CB1 −/−CB2 −/− mice. Furthermore, Δ9-THC synergized with the calcium ionophore, ionomycin, to increase CD69 expression on both CD4+ and CD8+ cells. In addition, without stimulation, Δ9-THC increased CD69 expression in CD8+ cells from CB1 −/−CB2 −/− and WT mice. Overall, these results suggest that CB1 and CB2 are dispensable for Δ9-THC-mediated suppression and that perturbation of Ca2+ signals during Tcell activation plays an important role in the mechanism by which Δ9-THC suppresses CTL function.

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Section: Discussionmentioning

confidence: 99%

Δ9-Tetrahydrocannabinol Suppresses Cytotoxic T Lymphocyte Function Independent of CB1 and CB2, Disrupting Early Activation Events

Karmaus¹,

Chen²,

Kaplan

et al. 2011

J Neuroimmune Pharmacol

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“…Ouabain, in vitro , inhibits mitogen-induced thymocyte and lymphocyte proliferation [10, 11], inhibits the generation of lymphokine-activated killer (LAK) activity induced by IL-2 [12], increases intracellular calcium levels [13], increases CD69 expression [14] and acts both in vitro [15] and in vivo [16] synergistically with corticoids. In vitro , ouabain increases glucocorticoid-induced plasma membrane depolarization in lymphoid cells [9].…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory and Antinociceptive Activity of Ouabain in Mice

Vasconcelos

Leite

Carneiro

et al. 2011

Mediators of Inflammation

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Ouabain, an inhibitor of the Na+/K+-ATPase pump, was identified as an endogenous substance of human plasma. Ouabain has been studied for its ability to interfere with various regulatory mechanisms. Despite the studies portraying the ability of ouabain to modulate the immune response, little is known about the effect of this substance on the inflammatory process. The aim of this work was to study the effects triggered by ouabain on inflammation and nociceptive models. Ouabain produced a reduction in the mouse paw edema induced by carrageenan, compound 48/80 and zymosan. This anti-inflammatory potential might be related to the inhibition of prostaglandin E2, bradykinin, and mast-cell degranulation but not to histamine. Ouabain also modulated the inflammation induced by concanavalin A by inhibiting cell migration. Besides that, ouabain presented antinociceptive activity. Taken these data together, this work demonstrated, for the first time, that ouabain presented in vivo analgesic and anti-inflammatory effects.

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“…In thymocytes, activation of the p38 pathway leads to the arrest of cell cycle progression and inhibition of differentiation of double negative thymocytes at the CD25 þ CD44 À stage (Diehl et al, 2000). Ouabain in vitro can inhibit mitogen-induced thymocyte proliferation (Szamel et al, 1981), increase intracellular calcium levels , increase CD69 expression (Rodrigues-Mascarenhas et al, 2003) and act both in vitro (Mann et al, 2001) and in vivo (Rodrigues-Mascarenhas et al, 2006) synergistically with corticoids. Ouabain is a specific inhibitor of the Na þ /K þ -ATPase; however, ouabain may not only regulate ion transport by Na þ / K þ -ATPase, but is also capable of inducing the activation of various signal transduction cascades (Xie, 2001;Harwood and Yaqoob, 2005).…”

Section: Introductionmentioning

confidence: 99%

Ouabain inhibits p38 activation in thymocytes

Rodrigues‐Mascarenhas¹,

Bloise²,

Moscat³

et al. 2008

Cell Biology International

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The MAPK p38 is phosphorylated by multiple stimuli and regulates a number of transcription factors. It is reported that activation of p38 leading to the regulation of NFAT may result from an alternative MKK-independent mechanism. This alternative pathway involves the protein Dlgh1 as an essential scaffold that assembles a module for the activation of p38. Ouabain, a specific inhibitor of the Na+/K+-ATPase, is capable of inducing the activation of various signal transduction cascades. In the present work, P-p38 levels of ConA-activated thymocytes treated with ouabain (1, 10 and 100 nM) were measured as also the effect of ouabain on NFATc1 expression. p38 phosphorylation and NFATc1 levels were analyzed by flow cytometry. The results indicated that ouabain inhibited both ConA-dependent increase in P-p38 and NFATc1 levels, which suggests an effect of ouabain on the p38 alternative pathway.

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CD69 expression induced by thapsigargin, phorbol ester and ouabain on thymocytes is dependent on external Ca2+ entry

Cited by 26 publications

References 39 publications

Δ9-Tetrahydrocannabinol Suppresses Cytotoxic T Lymphocyte Function Independent of CB1 and CB2, Disrupting Early Activation Events

Δ9-Tetrahydrocannabinol Suppresses Cytotoxic T Lymphocyte Function Independent of CB1 and CB2, Disrupting Early Activation Events

Anti-inflammatory and Antinociceptive Activity of Ouabain in Mice

Ouabain inhibits p38 activation in thymocytes

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