Inhibitor of sarco-endoplasmic reticulum Ca2+-ATPase thapsigargin stimulates production of nitric oxide and secretion of interferon-gamma

Kmoníčková, Eva; Melkusová, Petra; Harmatha, Juraj; Vokáč, Karel; Farghali, Hassan; Zı́dek, Zdeňek

doi:10.1016/j.ejphar.2008.03.037

Cited by 23 publications

(16 citation statements)

References 64 publications

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“…All used ANP were checked for lipopolysaccharide (LPS) to exclude possible bacterial contamination using chromogenic Limulus Amoebocyte Lysate assay (Kinetic-QCL; BioWhittaker, Walkersville, MD, USA). The highest 100 μM concentrations of ANP in culture wells contained less than 10 pg/ml of LPS, an amount that is ineffective to activate NO production and cytokine secretion [8]. LPS (Escherichia coli O111:B4) and rat recombinant IFN-γ used in experiments were purchased from Sigma (Prague, Czech Republic).…”

Section: Acyclic Nucleoside Phosphonates and Other Chemicalsmentioning

confidence: 99%

Differential effects of acyclic nucleoside phosphonates on nitric oxide and cytokines in rat hepatocytes and macrophages

Kostecká

Holý

Farghali

et al. 2012

International Immunopharmacology

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Section: Acyclic Nucleoside Phosphonates and Other Chemicalsmentioning

confidence: 99%

Differential effects of acyclic nucleoside phosphonates on nitric oxide and cytokines in rat hepatocytes and macrophages

Kostecká

Holý

Farghali

et al. 2012

International Immunopharmacology

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“…The myotubes were then resuspended in calcium-free medium, and TG or AVP was used to empty the SR. Calcium was then added back to the system at a concentration of 1.8 mM. TG depletes calcium stores by inhibiting sarco(endo)plasmic reticulum calcium-ATPase (SERCA) in muscle cells (35). Vasopressin depletes calcium stores by a G protein-coupled receptor mechanism that activates the SR inositol 1,4,5-trisphosphate (IP 3 ) receptor (21).…”

Section: Soce Regulates Intracellular Calcium Levels In L6 Myotubesmentioning

confidence: 99%

Dexamethasone stimulates store-operated calcium entry and protein degradation in cultured L6 myotubes through a phospholipase A₂-dependent mechanism

Itagaki

Menconi

Antoniu

et al. 2010

American Journal of Physiology-Cell Physiology

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Hasselgren PO. Dexamethasone stimulates store-operated calcium entry and protein degradation in cultured L6 myotubes through a phospholipase A 2-dependent mechanism. Am J Physiol Cell Physiol 298: C1127-C1139, 2010. First published January 27, 2010; doi:10.1152/ajpcell.00309.2009.-Muscle wasting in various catabolic conditions is at least in part regulated by glucocorticoids. Increased calcium levels have been reported in atrophying muscle. Mechanisms regulating calcium homeostasis in muscle wasting, in particular the role of glucocorticoids, are poorly understood. Here we tested the hypothesis that glucocorticoids increase intracellular calcium concentrations in skeletal muscle and stimulate storeoperated calcium entry (SOCE) and that these effects of glucocorticoids may at least in part be responsible for glucocorticoid-induced protein degradation. Treatment of cultured myotubes with dexamethasone, a frequently used in vitro model of muscle wasting, resulted in increased intracellular calcium concentrations determined by fura-2 AM fluorescence measurements. When SOCE was measured by using calcium "add-back" to muscle cells after depletion of intracellular calcium stores, results showed that SOCE was increased 15-25% by dexamethasone and that this response to dexamethasone was inhibited by the store-operated calcium channel blocker BTP2. Dexamethasone treatment stimulated the activity of calcium-independent phospholipase A 2 (iPLA2), and dexamethasone-induced increase in SOCE was reduced by the iPLA 2 inhibitor bromoenol lactone (BEL). In additional experiments, treatment of myotubes with the store-operated calcium channel inhibitor gadolinium ion or BEL reduced dexamethasone-induced increase in protein degradation. Taken together, the results suggest that glucocorticoids increase calcium concentrations in myocytes and stimulate iPLA 2-dependent SOCE and that glucocorticoid-induced muscle protein degradation may at least in part be regulated by increased iPLA 2 activity, SOCE, and cellular calcium levels. glucocorticoids; muscle; wasting MUSCLE WASTING, mainly reflecting stimulated degradation of myofibrillar proteins, is commonly seen in patients with sepsis, severe injury, and cancer (24, 52). Loss of muscle mass also occurs in patients with muscular dystrophy (30, 31). In previous studies, we found evidence (4, 15, 79) that sepsis-induced muscle proteolysis was associated with increased uptake and tissue levels of calcium in skeletal muscle. Additional reports suggest that muscle atrophy caused by other catabolic conditions, including denervation, burn injury, and muscular dystrophy, is also associated with increased tissue concentrations of calcium (2,3,10,17,64,73). These observations are significant because calcium is an important regulator of muscle protein balance and may link systemic catabolic responses to stimulated protein breakdown in skeletal muscle (16,34,50). The mechanisms regulating calcium entry and cellular levels of calcium in muscle-wasting conditions are not known.Glucocorticoids are prom...

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“…TGN, however, came to attention in recent years since the development of TGN analogue-based prodrug for the treatment of solid tumors (20). TGN has been known to increase cytokine production in macrophages and DCs (910111221). The effects of TGN on cytokine production by T cells are not clearly defined yet.…”

Section: Resultsmentioning

confidence: 99%

“…Much like ionomycin, TGN induces the activation of several intracellular signaling pathways, resulting in the production of a variety of cytokines. TGN elevates the production of IL-6 from mouse peritoneal macrophages (8), interferon-gamma (IFN-γ), IL-1β, and IL-6 from lipopolysaccharide (LPS)-stimulated rat peritoneal macrophages (9), tumor necrosis factor-α and IL-6 from LPS-activated macrophages (10), IFN-γ from murine macrophages and human peripheral blood mononuclear cells (11), and IL-6 from bone marrow-derived dendritic cells (DCs) (12). TGN has also been reported to inhibit the production of nitric oxide, IL-10, and RANTES in macrophages stimulated with LPS, or LPS plus IFN-γ (13).…”

Section: Introductionmentioning

confidence: 99%

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

Kim

Jung

et al. 2018

Immune Netw

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Thapsigargin (TGN) is a potent and selective inhibitor of sarco-endoplasmic Ca2+-ATPase, leading to rapid elevation of cytoplasmic Ca2+ concentration. Previous reports have shown that TGN increases the production of various cytokines from macrophages and dendritic cells. Here, we examine the effects of TGN on murine T cells. Nanomolar concentrations of TGN are a significant inducer of IL-2 production with full activity at 50 nM. Micromolar concentrations of TGN, however, are inhibitory to IL-2 production and T cell proliferation. The IL-2 production-inducing activity of TGN is much more prominent when T cells are primed with concanavalin A or anti-CD3 mAb, and is due to the increase of cytoplasmic Ca2+ concentration. TGN at 50 nM does not affect interferon-gamma or IL-4 production from T cells. Thus, the present study shows that low nanomolar concentrations of TGN could be useful in potentiating IL-2 production from antigen-primed T cells.

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Inhibitor of sarco-endoplasmic reticulum Ca2+-ATPase thapsigargin stimulates production of nitric oxide and secretion of interferon-gamma

Cited by 23 publications

References 64 publications

Differential effects of acyclic nucleoside phosphonates on nitric oxide and cytokines in rat hepatocytes and macrophages

Differential effects of acyclic nucleoside phosphonates on nitric oxide and cytokines in rat hepatocytes and macrophages

Dexamethasone stimulates store-operated calcium entry and protein degradation in cultured L6 myotubes through a phospholipase A₂-dependent mechanism

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

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Inhibitor of sarco-endoplasmic reticulum Ca2+-ATPase thapsigargin stimulates production of nitric oxide and secretion of interferon-gamma

Cited by 23 publications

References 64 publications

Differential effects of acyclic nucleoside phosphonates on nitric oxide and cytokines in rat hepatocytes and macrophages

Differential effects of acyclic nucleoside phosphonates on nitric oxide and cytokines in rat hepatocytes and macrophages

Dexamethasone stimulates store-operated calcium entry and protein degradation in cultured L6 myotubes through a phospholipase A2-dependent mechanism

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

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Dexamethasone stimulates store-operated calcium entry and protein degradation in cultured L6 myotubes through a phospholipase A₂-dependent mechanism