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 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.
Uemura
Yasushi
Y
Department of Allergy and Immunology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama, Saitama 350-0495, Japan. uemura@saitama-med.ac.jp
Liu
Tian-Yi
TY
Narita
Yayoi
Y
Suzuki
Motoharu
M
Ohshima
Susumu
S
Mizukami
Satoshi
S
Ichihara
Yasuko
Y
Kikuchi
Hirosato
H
Matsushita
Sho
S
D051940:B7-2 Antigen / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D003408:Cresols / Q000494:pharmacology; D003620:Dantrolene / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics* / Q000378:metabolism
D051940:B7-2 Antigen; D002614:Chelating Agents; D003408:Cresols; D006684:HLA-DR Antigens; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D019837:Ryanodine Receptor Calcium Release Channel; D016753:Interleukin-10; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; C006984:chlorocresol; D004533:Egtazic Acid; D003620:Dantrolene; D002118:Calcium