TCRzeta mRNA splice variant forms observed in the peripheral blood T cells from systemic lupus erythematosus patients.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown etiology. Tyrosine phosphorylation and protein expression of the T-cell receptor zeta chain (zeta) have been reported to be significantly decreased in SLE T cells. In addition, zeta mRNA with alternatively spliced 3' untranslated region (zetamRNA/as-3'UTR) is detected predominantly in SLE T cells, and aberrant zeta mRNA accompanied by the mutations in the open reading frame including zeta mRNA lacking exon7 (zetamRNA/exon7-) is observed in SLE T cells. These zeta mRNA splice variant forms exhibit a reduction in the expression of TCR/CD3 complex and zeta protein on their cell surface due to the instability of zeta mRNA splice variant forms as well as the reduction in interleukin (IL)-2 production after stimulating with anti-CD3 antibody. Data from cDNA microarray showed that 36 genes encoding cytokines and chemokines, including IL-2, IL-15, IL-18, and TGF-beta2, were down-regulated in the MA5.8 cells transfected with the zeta mRNA splice variant forms. Another 16 genes were up-regulated and included genes associated with membranous proteins and cell damage granules, including the genes encoding poliovirus-receptor-related 2, syndecan-1, and granzyme A.
Tsuzaka
Kensei
K
Division of Rheumatology, Department of Internal Medicine, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama, 350-8550, Japan. kentsu@saitama-med.ac.jp
Nozaki
Kyoko
K
Kumazawa
Chika
C
Shiraishi
Kiyono
K
Setoyama
Yumiko
Y
Yoshimoto
Keiko
K
Abe
Tohru
T
Takeuchi
Tsutomus
T
D020413:3' Untranslated Regions / Q000235:genetics / Q000276:immunology; D017398:Alternative Splicing / Q000235:genetics* / Q000276:immunology; D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005091:Exons / Q000235:genetics / Q000276:immunology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics* / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
D020413:3' Untranslated Regions; D016207:Cytokines; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell