Abnormal activation of the Akt-GSK3beta signaling pathway in peripheral blood T cells from patients with systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease accompanied by the activation and proliferation of T cells and B cells. In this study, we found that the distributions of lymphocytes obtained from patients with SLE or SLE with renal disease (RSLE) were reduced in the G(0)/G(1) phase and were elevated in the S phase after phytohemagglutinin treatment. Increased expression of CDK2 and decreased expression of cyclin-dependent kinase inhibitors p27(Kip1) and p21(WAF1/CIP1) were observed in RSLE and SLE lymphocytes. The phosphorylation levels of Akt473 and GSK3beta (ser9) were increased in lymphocytes from the patients. Moreover, inhibition of GSK3beta with lithium chloride or SB216763 induced T cell proliferation, and the most significant effects were observed in RSLE lymphocytes. These results indicate that upregulation of CDKs and downregulation of p27(Kip1) and p21(WAF1/CIP1) increased the proliferation of T lymphocytes in SLE patients. Abnormal activation of the Akt-GSK3beta signaling pathway increased the proliferation of lupus lymphocytes.
Tang
Hongfeng
H
Department of Dermatology, Second Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Tan
Guozhen
G
Guo
Qing
Q
Pang
Ruiping
R
Zeng
Fanqin
F
D002478:Cells, Cultured; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D016193:G1 Phase; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology* / Q000276:immunology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D016192:Resting Phase, Cell Cycle; D016196:S Phase; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology
D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D038362:Glycogen Synthase Kinase 3