Induction of heme oxygenase-1 in normal and malignant B lymphocytes by 15-deoxy-Delta(12,14)-prostaglandin J(2) requires Nrf2.
Heme-oxygenase-1 (HO-1) is induced in response to oxidative stress and is believed to be a cytoprotective and anti-inflammatory enzyme. It is unknown whether normal or malignant human B-lineage cells express HO-1. 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is an interesting electrophilic lipid mediator able to increase oxidative stress in B cells. Here, we tested normal and malignant human B-lineage cells for their ability to express HO-1 in response to 15d-PGJ(2), as well as the signaling pathways required for HO-1 expression. 15d-PGJ(2) potently induced HO-1 protein expression in normal and malignant B cells. Malignant B cells exhibited a greater induction of HO-1 protein compared to normal B lymphocytes. Using siRNA directed against the transcription factor Nrf2 and B cells isolated from Nrf2-deficient mice, we show that HO-1 induction by 15d-PGJ(2) is dependent on Nrf2. These results show that, compared to normal B lymphocytes, malignant B cells have a greater capacity to increase their HO-1 protein levels in response to 15d-PGJ(2). We speculate that the ability to highly express HO-1 by malignant B cells could confer a survival advantage.
Bancos
Simona
S
Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Baglole
Carolyn J
CJ
Rahman
Irfan
I
Phipps
Richard P
RP
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D015448:Leukemia, B-Cell / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000276:immunology; D034741:RNA, Small Interfering / Q000235:genetics; D014158:Transcription, Genetic
C477819:15-deoxyprostaglandin J2; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C495636:Nfe2l2 protein, mouse; D034741:RNA, Small Interfering; D051547:Heme Oxygenase-1; D015230:Prostaglandin D2