1. Signal transduction mechanism of the NZW type IL‑10R1 and the effect on B lymphocyte function
- Author
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Cheng Diao, Zanmei Qi, Yi Jiang, Shuyan Du, and Xinzhe Cai
- Subjects
STAT3 Transcription Factor ,Cancer Research ,Lymphocyte ,Interleukin-10 Receptor alpha Subunit ,Biology ,Biochemistry ,Cell Line ,Mice ,Genetics ,medicine ,Animals ,Humans ,Lupus Erythematosus, Systemic ,L-Selectin ,Phosphorylation ,STAT3 ,Molecular Biology ,TYK2 Kinase ,B-Lymphocytes ,Janus kinase 1 ,Cell growth ,Interleukin ,Transfection ,Janus Kinase 1 ,Cell biology ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Oncology ,Cell culture ,Mutagenesis ,biology.protein ,Molecular Medicine ,Signal transduction ,Signal Transduction - Abstract
The present study aimed to investigate the signal transduction mechanism of the NZW type interleukin (IL)‑10R1 and the effect on the function of B lymphocytes. Vectors for the expression of wild‑type, NZW and G1146A IL‑10R1 were constructed and transfected into Ba/F3 cells. The cell proliferation curve was determined using an MTT assay. CD32 and leukocyte-endothelial cell adhesion molecule 1 (LECAM‑1) expression levels were assessed using flow cytometry. The phosphorylation of Janus kinase 1 (Jak1), tyrosine kinase 2 (Tyk2) and signal transducer and activator of transcription 3 (Stat3) were measured by western blot analysis. As compared with wild‑type IL‑10R1 cells, the proliferation ability of NZW IL‑10R1 cells was increased following stimulation with IL‑10, which was even greater for G1146A cells. CD32 levels in NZW IL‑10R1 cells were lower, while the expression of LECAM‑1 was higher compared with wild‑type IL‑10R1 cells, which was also observed for G1146A cells. The phosphorylation levels of Jak1 and Stat3 in NZW IL‑10R1 and G1146A IL‑10R1 cells were significantly lower compared with the wild‑type IL‑10R1 cells. However, the phosphorylation levels in the three cell types were not significantly different. In conclusion, the deficiency in Jak1‑Stat3 signal transduction in NZW IL‑10R1 cells induces a loss in the inhibition ability of proliferation and activation as well as a migration tendency of B lymphocytes, which is hypothesized to be associated with the occurrence and development of the autoimmune disease systemic lupus erythematosus (SLE).
- Published
- 2013