Thapsigargin Increases IL-2 Production in T Cells at Nanomolar Concentrations

Kim, Ki-Hyang; Kim, Sang-Hyun; Jung, Ho-Hyun; Moon, Jun-Hyeok; Jeong, Seong-Un; Yu, Kyeongae; Lee, Chong-Kil

doi:10.4110/in.2018.18.e26

Cited by 4 publications

(2 citation statements)

References 24 publications

(29 reference statements)

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“…T cells were seeded at a density of ∼ 50,000 cells/well and activated using two models: (i) PMA (10 ng/mL) and Ionomcyin (0.1 or 0.5 μM) or Thapsigargin (0.01 or 0.05 μM), a TCR-independent activation model, to recapitulate optimal and high calcium levels (13,14) (ii) plate bound anti-mouse CD3 and soluble anti-mouse CD28, a TCR-dependent activation model (8,15). For anti-CD3/anti-CD28 based activation, 96 well U-bottomed plates (Corning, USA) were coated with 0.5 μg/mL of hamster anti-mouse CD3 (eBioscience, USA) and incubated overnight at 4°C (8).…”

Section: Methodsmentioning

confidence: 99%

High intracellular calcium amounts inhibit activation-induced proliferation of mouse T cells

Joseph,

Kumar,

Chatterjee

et al. 2024

Preprint

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Optimal T cell activation is critical to orchestrate adaptive immune responses. Calcium is critical for T cell activation and integrates signaling pathways necessary to activate key transcription factors. In fact, patients with calcium channelopathies are immunodeficient. Here, we investigated the effects of different concentrations of intracellular calcium on activation of mouse T cells. High intracellular calcium amounts inhibitedin vitroT cell proliferation as evidenced by a decreased cell cycling-to-hypodiploidy ratio in two models of activation: the combination of phorbol 12-myristate 13-acetate (PMA) and Ionomycin (an ionophore)/Thapsigargin (a SERCA inhibitor) or plate bound anti-CD3 and anti-CD28. High intracellular calcium amounts increased the production of reactive oxygen species (ROS) in T cells activated with PMA and Ionomycin and scavenging excess ROS using N-acetyl cysteine (NAC) or PEGylated superoxide dismutase (PEG-SOD) rescued the decrease in cycling-to-hypodiploidy ratio. To test the universality of our observations, we studied the effects of tert-Butylhydroquinone (tBHQ), a SERCA inhibitor and Nrf2 activator. tBHQ alone did not increase intracellular calcium amounts but increase was observed along with PMA. Also, tBHQ inhibited T cell activation in a dose-dependent manner in bothin vitromodels of T cell activation. Importantly, intraperitoneal injection of tBHQ ameliorated Dextran Sodium Sulfate (DSS)-induced colitis in mice as evidenced by rescue of colon length shortening and lower disease activity index. Overall, this study identifies high calcium amounts as a potential target to lower T cell activation. The implications of these observations are discussed as this strategy may be important in treatment of some autoimmune diseases.

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Section: Methodsmentioning

confidence: 99%

High intracellular calcium amounts inhibit activation-induced proliferation of mouse T cells

Joseph,

Kumar,

Chatterjee

et al. 2024

Preprint

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“…Specifically, both sesquiterpenes induce secretion of interferon-γ ,− and IL-2 in macrophages in submicromolar or low micromolar concentrations. Currently, Kim et al have published results on T cells stimulated by compound 1 . In this type of immune cell, compound 1 is inducer of IL-2 at nanomolar concentrations.…”

Section: Terpenoid Serca Inhibitorsmentioning

confidence: 99%

Sarco/Endoplasmic Reticulum Calcium ATPase Inhibitors: Beyond Anticancer Perspective

et al. 2020

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The sarco/endoplasmic reticulum calcium ATPase (SERCA), which plays a key role in the maintenance of Ca 2+ ion homeostasis, is an extensively studied enzyme, the inhibition of which has a considerable impact on cell life and death decision. To date, several SERCA inhibitors have been thoroughly studied and the most notable one, a derivative of the sesquiterpene lactone thapsigargin, is gradually approaching a clinical application. Meanwhile, new compounds with SERCA-inhibiting properties of natural, synthetic, or semisynthetic origin are being discovered and/or developed; some of these might also be suitable for the development of new drugs with improved performance. This review brings an up-to-date comprehensive overview of recently discovered compounds with the potential of SERCA inhibition, discusses their mechanism of action, and highlights their potential clinical applications, such as cancer treatment.

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7-Hydroxy Frullanolide, a sesquiterpene lactone, increases intracellular calcium amounts, lowers CD4+ T cell and macrophage responses, and ameliorates DSS-induced colitis

Pathak

Gokhroo

Dubey

et al. 2021

International Immunopharmacology

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Thapsigargin Increases IL-2 Production in T Cells at Nanomolar Concentrations

Cited by 4 publications

References 24 publications

High intracellular calcium amounts inhibit activation-induced proliferation of mouse T cells

High intracellular calcium amounts inhibit activation-induced proliferation of mouse T cells

Sarco/Endoplasmic Reticulum Calcium ATPase Inhibitors: Beyond Anticancer Perspective

7-Hydroxy Frullanolide, a sesquiterpene lactone, increases intracellular calcium amounts, lowers CD4+ T cell and macrophage responses, and ameliorates DSS-induced colitis

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