Identification of functional type 1 ryanodine receptors in human dendritic cells

Ryanodine receptor (RyR) is a Ca 2+ channel that mediates Ca 2+ release from intracellular stores. Altered Ca 2+ homeostasis in skeletal muscle which usually occurs as a result of point mutations in type 1 RyR1 (RyR1) is a key molecular event triggering malignant hyperthermia (MH). There are three R...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2007-10, Vol.362 (2), p.510-515
Main Authors: Uemura, Yasushi, Liu, Tian-Yi, Narita, Yayoi, Suzuki, Motoharu, Ohshima, Susumu, Mizukami, Satoshi, Ichihara, Yasuko, Kikuchi, Hirosato, Matsushita, Sho
Format: Article
Language:English
Subjects:
B7-2 Antigen - metabolism
Biological Transport - drug effects
Calcium - metabolism
Chelating Agents - pharmacology
Cresols - pharmacology
Dantrolene - pharmacology
Dendritic cells
Dendritic Cells - cytology
Dendritic Cells - drug effects
Dendritic Cells - metabolism
Egtazic Acid - analogs & derivatives
Egtazic Acid - pharmacology
Enzyme-Linked Immunosorbent Assay
Gene Expression
HLA-DR Antigens - metabolism
Humans
Interleukin-10 - metabolism
Lipopolysaccharides - pharmacology
Malignant hyperthermia
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
RNA, Messenger - metabolism
Ryanodine receptor
Ryanodine Receptor Calcium Release Channel - genetics
Ryanodine Receptor Calcium Release Channel - metabolism
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Summary:Ryanodine receptor (RyR) is a Ca 2+ channel that mediates Ca 2+ release from intracellular stores. Altered Ca 2+ homeostasis in skeletal muscle which usually occurs as a result of point mutations in type 1 RyR1 (RyR1) is a key molecular event triggering malignant hyperthermia (MH). There are three RyR isoforms, and we herein show, for the first time, that human dendritic cells (DCs) preferentially express RyR1 mRNA among them. The RyR activator, 4-chloro- m-cresol (4CmC), induced Ca 2+ release in DCs, and this response was eliminated by dantrolene, an inhibitor of the RyR1, and was unaffected by xestospongin C, a selective inhibitor of IP 3 receptor. Activation of RyR1 reduced LPS-induced IL-10 production, promoted the expression of HLA-DR and CD86, and thereby exhibited an improved capacity to stimulate allogeneic T cells. These findings demonstrate that RyR1-mediated calcium signaling modifies diverse DC responses and suggest the feasibility of using DC preparations for the diagnosis of MH.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2007.08.024