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The Role of p38 Mitogen‐Activated Protein Kinase in Regulating Interleukin‐10 Gene Expression in Burkitt's Lymphoma Cell Lines
Author(s) -
Horie Kazutaka,
Ohashi Makoto,
Satoh Yukio,
Sairenji Takeshi
Publication year - 2007
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/j.1348-0421.2007.tb03885.x
Subject(s) - biology , microbiology and biotechnology , mapk/erk pathway , p38 mitogen activated protein kinases , cell culture , downregulation and upregulation , burkitt's lymphoma , protein kinase a , kinase , gene expression , cancer research , gene , biochemistry , genetics
In malignant B lymphoma cells interleukin‐10 (IL‐10) expression is frequently upregulated. This effect is thought to support to the malignant transformation of these cells and to be a potential target for pharmacotherapy. To define better the mechanism for upregulation of the IL‐10 gene, we tested the association between IL‐10 and p38 mitogen‐activated protein kinase (MAPK) in several Epstein‐Barr virus (EBV) infected and non‐infected Burkitt's lymphoma (BL) cell lines. The all BL cell lines expressed IL‐10 and IL‐10 receptor mRNAs, and produced IL‐10. p38 MAPK was constitutively phosphorylated in the cytoplasm of the BL cell lines. We further analyzed molecular effects of p38 MAPK on IL‐10 expression in Akata cells. Exogenous IL‐10 lead rapidly to phosphorylation of Jak1 and Tyk2 as transducers of signals of IL‐10, and promoted growth of Akata cells in a dose‐dependent manner. The phosphorylation of cytoplasmic p38 MAPK in Akata cells was reduced by the serine/threonine kinase inhibitor, 1‐(5‐isoquinolinesulfonyl)‐2‐methylpiperazine (H7). A specific inhibitor of p38 MAPK, SB203580, blocked simultaneously STAT3 DNA‐binding activity, and IL‐10 mRNA expression, IL‐10 production, and then the cell growth was inhibited. These results indicate that the p38 MAPK pathway is functionally linked to IL‐10 gene expression and supports the view that the constitutive activation of cytoplasmic p38 MAPK in BL cells is a step in the upregulation of IL‐10 gene expression and lymphomagenesis.