Identification of downstream genes up-regulated by the tumor necrosis factor family member TALL-1.
TALL-1 is a member of the tumor necrosis factor family that binds to BCMA, TACI, and BAFF-R, three receptors mostly expressed by mature B lymphocytes. Previous studies have shown that the TALL-1 signaling is critically involved in B cell proliferation, maturation, and progression of lupus-like, autoimmune diseases. In this report, we performed cDNA subtractive hybridization experiments to identify downstream genes up-regulated by TALL-1. These experiments indicated that 10 genes, including interleukin (IL)-10, lymphocyte activation gene-1 (LAG-1), GCP-2, PBEF, ferritin, PIM-2, TFG, CD27 ligand, DUSP5, and archain, were up-regulated at the mRNA level by TALL-1 stimulation in B lymphoma RPMI-8226 cells and/or primary B lymphocytes. We also demonstrated that TALL-1 activated transcription of IL-10 and LAG-1 in a nuclear factor-kappaB-dependent manner in reporter gene assays. Moreover, our findings indicated BAFF-R, but not TACI, could dramatically up-regulate IL-10 secretion by RPMI-8226 cells. The identification of TALL-1-up-regulated genes will help explain the mechanisms of TALL-1-triggered biological and pathological effects and to identify molecular targets for intervention of lupus-like autoimmune diseases.
Xu
Liang-Guo
LG
Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver 80206, USA.
Wu
Min
M
Hu
Jiancheng
J
Zhai
Zhonghe
Z
Shu
Hong-Bing
HB
D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; D001402:B-Lymphocytes / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000494:pharmacology / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D014411:Neoplastic Stem Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D018124:Receptors, Tumor Necrosis Factor / Q000187:drug effects / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D015398:Signal Transduction; D013382:Subtraction Technique; D014158:Transcription, Genetic / Q000187:drug effects; D053303:Transmembrane Activator and CAML Interactor Protein; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*
D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; D018076:DNA, Complementary; D008565:Membrane Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; C108467:TNFRSF13B protein, human; C435926:TNFRSF13C protein, human; C086966:TNFRSF17 protein, human; C505719:TNFSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein; D014409:Tumor Necrosis Factor-alpha