Synergistic effect of interleukin-6 and endoplasmic reticulum stress inducers on the high level of ABCG2 expression in plasma cells.
ABCG2 is a transporter preferentially expressed in a primitive subpopulation of cells and recently reported as a surviving factor for trophoblasts. To date, manner of ABCG2 expression in lymphoid tissues is not known. Immunohistochemically, strong ABCG2 expression was found in a small proportion of plasma cells mainly located in the interfollicular space of lymphoid tissues. The number of ABCG2-high plasma cells increased in interleukin-6- (IL-6) rich lesions, such as Castleman's disease of plasma cell type. Plasma cells are subjected to endoplasmic reticulum (ER) stress when excess proteins are synthesized, and IL-6 stimulates protein synthesis. Therefore, the effect of IL-6 and ER stress on ABCG2 expression in plasma cells was examined. The expression level of ABCG2 increased by treatment with either IL-6 or ER stress inducers, and further increased with both. The promoter analysis revealed that the effect of IL-6 and ER stress inducers was mediated through the site overlapping XBP-1 and HIF-1 binding sequences. Knocked-down of ABCG2 by siRNA or ABCG2 inhibitor reduced plasma cell viability under ER stress. These suggest that ABCG2 is a surviving factor for plasma cells. To our knowledge, this is the first study reporting the effect of ER stress on ABCG2 expression.
Nakamichi
Naoto
N
Department of Pathology, Graduate School of Medicine, Osaka University, Osaka, Japan.
Morii
Eiichi
E
Ikeda
Jun-ichiro
J
Qiu
Ying
Y
Mamato
Suhana
S
Tian
Tian
T
Fukuhara
Shirou
S
Aozasa
Katsuyuki
K
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D019175:DNA Methylation / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008223:Lymphoma / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D014066:Palatine Tonsil / Q000378:metabolism / Q000473:pathology; D010950:Plasma Cells / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D013312:Stress, Physiological; D019284:Thapsigargin / Q000494:pharmacology; D014415:Tunicamycin / Q000494:pharmacology
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D015850:Interleukin-6; D009363:Neoplasm Proteins; D014415:Tunicamycin; D019284:Thapsigargin; D053148:Caspase 3