β-Endorphin modulates T-cell intracellular calcium flux and c-myc expression via a potassium channel

Abstract Patients who undergo allogeneic bone marrow transplantation (BMT) are clinically immunodeficient for a prolonged period after engraftment. In the present study, we examined immune function after BMT in a series of patients who had received HLA compatible sibling marrow grafts purged of T cells with anti-CD6 monoclonal antibody and complement. None of the patients in this analysis received immunomodulating agents and none had developed graft-versus-host disease (GVHD). Initially after BMT, natural killer (NK) cells are the predominant cell type, giving way to CD3+, CD5+ T cells after 4 to 8 weeks. Despite the return of normal numbers of T lymphocytes post-BMT phenotypic analysis reveals several long-term abnormalities, including an inverted T4:T8 ratio and a significant fraction of CD3+ T cells that do not co-express CD6. In mitogenic assays, stimulation by either nonspecific lectin (phytohemagglutinin; PHA) or antibodies to the CD2 surface structure (anti-T11(2) + anti-T11(3)) results in decreased levels of T-cell proliferation compared with controls for over 18 months post-BMT. In contrast, the ability of unstimulated peripheral blood mononuclear cells (PBMC) to respond to recombinant interleukin-2 (rIL-2) is relatively intact, most likely reflecting early functional reconstitution of the NK cell population. To further characterize the prolonged abnormalities in T-cell proliferation after PHA or CD2 stimulation, we examined more proximal events in T-cell activation such as induction of IL-2 receptor expression and stimulus-induced intracellular calcium flux. We found that the induction of IL-2 receptor (p55) after in vitro activation, although initially abnormal, recovers completely by 6 months post-BMT. We also found that, after CD2 stimulation, calcium flux in T cells was normal immediately after engraftment. In contrast, after stimulation with anti-CD3 antibodies, a large population of T cells do not develop intracellular calcium flux compared with controls. We conclude that despite the recovery of normal numbers of T lymphocytes early after engraftment of CD6-depleted marrow, these T cells exhibit several physiologic and functional abnormalities that persist for varying intervals post-BMT. At present, it is unclear which of these specific defects is most closely associated with increased susceptibility to infectious agents after BMT.

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Time dependence of transmembrane potential changes and intracellular calcium flux in stimulated human monocytes

Journal of Cellular Physiology ◽

10.1002/jcp.1041340116 ◽

1988 ◽

Vol 134 (1) ◽

pp. 131-136 ◽

Cited By ~ 13

Author(s):

John Bernardo ◽

Holly F. Brink ◽

Elizabeth R. Simons

Keyword(s):

Time Dependence ◽

Intracellular Calcium ◽

Transmembrane Potential ◽

Calcium Flux ◽

Human Monocytes ◽

Intracellular Calcium Flux

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Prostanglandin D2 modulates human neutrophil intracellular calcium flux and inhibits superoxide release via its ring carbonyl

Life Sciences ◽

10.1016/0024-3205(90)90067-2 ◽

1990 ◽

Vol 46 (11) ◽

pp. 793-801 ◽

Cited By ~ 6

Author(s):

Cuthbert O. Simpkins ◽

Denise L. Mazorow ◽

Sione T. Alailima ◽

Elin A. Tate ◽

William Sweatt ◽

...

Keyword(s):

Intracellular Calcium ◽

Human Neutrophil ◽

Calcium Flux ◽

Superoxide Release ◽

Intracellular Calcium Flux

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ZAP-70 enhances IgM signaling independent of its kinase activity in chronic lymphocytic leukemia

Blood ◽

10.1182/blood-2006-12-062265 ◽

2008 ◽

Vol 111 (5) ◽

pp. 2685-2692 ◽

Cited By ~ 93

Author(s):

Liguang Chen ◽

Lang Huynh ◽

John Apgar ◽

Li Tang ◽

Laura Rassenti ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

B Cell ◽

Intracellular Calcium ◽

Kinase Activity ◽

Cell Receptor ◽

Sh2 Domain ◽

Lymphocytic Leukemia ◽

Calcium Flux ◽

Response To Treatment ◽

Intracellular Calcium Flux

We transduced chronic lymphocytic leukemia (CLL) cells lacking ZAP-70 with vectors encoding ZAP-70 or various mutant forms of ZAP-70 and monitored the response of transduced CLL cells to treatment with F(ab)2 anti-IgM (anti-μ). CLL cells made to express ZAP-70, a kinase-defective ZAP-70 (ZAP-70-KA369), or a ZAP-70 unable to bind c-Cbl (ZAP-YF292) experienced greater intracellular calcium flux and had greater increases in the levels of phosphorylated p72Syk, B-cell linker protein (BLNK), and phospholipase C-γ, and greater activation of the Ig accessory molecule CD79b in response to treatment with anti-μ than did mock-transfected CLL cells lacking ZAP-70. Transfection of CLL cells with vectors encoding truncated forms of ZAP-70 revealed that the SH2 domain, but not the SH1 domain, was necessary to enhance intracellular calcium flux in response to treatment with anti-μ. We conclude that ZAP-70 most likely acts as an adapter protein that facilitates B-cell receptor (BCR) signaling in CLL cells independent of its tyrosine kinase activity or its ability to interact with c-Cbl.

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Reconstitution of T-cell function after CD6-depleted allogeneic bone marrow transplantation

Blood ◽

10.1182/blood.v75.10.2076.bloodjournal75102076 ◽

1990 ◽

Vol 75 (10) ◽

pp. 2076-2084 ◽

Cited By ~ 2

Author(s):

RJ Soiffer ◽

L Bosserman ◽

C Murray ◽

K Cochran ◽

J Daley ◽

...

Keyword(s):

Bone Marrow ◽

Cell Proliferation ◽

T Cells ◽

T Cell ◽

Allogeneic Bone Marrow Transplantation ◽

Calcium Flux ◽

T Cell Proliferation ◽

Allogeneic Bone ◽

Normal Numbers ◽

Intracellular Calcium Flux

Patients who undergo allogeneic bone marrow transplantation (BMT) are clinically immunodeficient for a prolonged period after engraftment. In the present study, we examined immune function after BMT in a series of patients who had received HLA compatible sibling marrow grafts purged of T cells with anti-CD6 monoclonal antibody and complement. None of the patients in this analysis received immunomodulating agents and none had developed graft-versus-host disease (GVHD). Initially after BMT, natural killer (NK) cells are the predominant cell type, giving way to CD3+, CD5+ T cells after 4 to 8 weeks. Despite the return of normal numbers of T lymphocytes post-BMT phenotypic analysis reveals several long-term abnormalities, including an inverted T4:T8 ratio and a significant fraction of CD3+ T cells that do not co-express CD6. In mitogenic assays, stimulation by either nonspecific lectin (phytohemagglutinin; PHA) or antibodies to the CD2 surface structure (anti-T11(2) + anti-T11(3)) results in decreased levels of T-cell proliferation compared with controls for over 18 months post-BMT. In contrast, the ability of unstimulated peripheral blood mononuclear cells (PBMC) to respond to recombinant interleukin-2 (rIL-2) is relatively intact, most likely reflecting early functional reconstitution of the NK cell population. To further characterize the prolonged abnormalities in T-cell proliferation after PHA or CD2 stimulation, we examined more proximal events in T-cell activation such as induction of IL-2 receptor expression and stimulus-induced intracellular calcium flux. We found that the induction of IL-2 receptor (p55) after in vitro activation, although initially abnormal, recovers completely by 6 months post-BMT. We also found that, after CD2 stimulation, calcium flux in T cells was normal immediately after engraftment. In contrast, after stimulation with anti-CD3 antibodies, a large population of T cells do not develop intracellular calcium flux compared with controls. We conclude that despite the recovery of normal numbers of T lymphocytes early after engraftment of CD6-depleted marrow, these T cells exhibit several physiologic and functional abnormalities that persist for varying intervals post-BMT. At present, it is unclear which of these specific defects is most closely associated with increased susceptibility to infectious agents after BMT.

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Heat induces interleukin-6 in skeletal muscle cells via TRPV1/PKC/CREB pathways

Journal of Applied Physiology ◽

10.1152/japplphysiol.00139.2016 ◽

2017 ◽

Vol 122 (3) ◽

pp. 683-694 ◽

Cited By ~ 9

Author(s):

Syotaro Obi ◽

Toshiaki Nakajima ◽

Takaaki Hasegawa ◽

Hironobu Kikuchi ◽

Gaku Oguri ◽

...

Keyword(s):

Skeletal Muscle ◽

Intracellular Calcium ◽

Interleukin 6 ◽

Transient Receptor Potential ◽

Signal Transduction Pathway ◽

Muscle Cells ◽

Skeletal Muscle Cells ◽

Calcium Flux ◽

Dependent Manner ◽

Intracellular Calcium Flux

Interleukin-6 (IL-6) is released from skeletal muscle cells and induced by exercise, heat, catecholamine, glucose, lipopolysaccharide, reactive oxygen species, and inflammation. However, the mechanism that induces release of IL-6 from skeletal muscle cells remains unknown. Thermosensitive transient receptor potential (TRP) proteins such as TRPV1–4 play vital roles in cellular functions. In this study we hypothesized that TRPV1 senses heat, transmits a signal into the nucleus, and produces IL-6. The purpose of the present study is to investigate the underlying mechanisms whereby skeletal muscle cells sense and respond to heat. When mouse myoblast cells were exposed to 37–42°C for 2 h, mRNA expression of IL-6 increased in a temperature-dependent manner. Heat also increased IL-6 secretion in myoblast cells. A fura 2 fluorescence dual-wavelength excitation method showed that heat increased intracellular calcium flux in a temperature-dependent manner. Intracellular calcium flux and IL-6 mRNA expression were increased by the TRPV1 agonists capsaicin and N-arachidonoyldopamine and decreased by the TRPV1 antagonists AMG9810 and SB366791 and siRNA-mediated knockdown of TRPV1. TRPV2, 3, and 4 agonists did not change intracellular calcium flux. Western blotting with inhibitors demonstrated that heat increased phosphorylation levels of TRPV1, followed by PKC and cAMP response element-binding protein (CREB). PKC inhibitors, Gö6983 and staurosporine, CREB inhibitors, curcumin and naphthol AS-E, and knockdown of CREB suppressed the heat-induced increases in IL-6. These results indicate that heat increases IL-6 in skeletal muscle cells through the TRPV1, PKC, and CREB signal transduction pathway.NEW & NOTEWORTHY Heat increases the release of interleukin-6 (IL-6) from skeletal muscle cells. IL-6 has been shown to serve immune responses and metabolic functions in muscle. It can be anti-inflammatory as well as proinflammatory. However, the mechanism that induces release of IL-6 from skeletal muscle cells remains unknown. Here we show that heat increases IL-6 in skeletal muscle cells through the transient receptor potential vannilloid 1, PKC, and cAMP response element-binding protein signal transduction pathway.

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