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- Title
Role of mitogen-activated protein kinase family in serum-induced leukaemia inhibitory factor and interleukin-k secretion by bone marrow stromal cells.
- Authors
Nakao, Takafumi; Kim, Shokei; Ohta, Kensuke; Kawano, Hitomi; Hino, Masayuki; Miura, Katsuyuki; Tatsumi, Noriyuki; Iwao, Hiroshi
- Abstract
1 In the haematopoietic microenvironment, bone marrow stromal cells play an important role in regulating haematopoiesis by expressing various cytokines, including leukaemia inhibitory factor (LIF) and interleukin-6 (IL-6). However, the intracellular signal that regulates cytokine secretion in bone marrow stromal cells has not been determined. The aim of this study was to evaluate the role of mitogen-activated protein kinase (MAPK) family in serum-induced secretion of LIF and IL-6 by bone marrow stromal cells. 2 Transformed human bone marrow stromal cells (HS-5) were stimulated with foetal calf serum (FCS) to produce LIF and IL-6. FCS also induced activation of extracellular signal-regulated kinase (ERK), p38 MAPK and c-Jun NH[sub 2]-terminal kinase (JNK). 3 Both PD98059 (MAPK/ERK kinase inhibitor) and SB203580 (p38 MAPK inhibitor) attenuated FCS-induced LIF protein production and gene expression. SB203580 decreased IL-6 production and gene expression, but PD98059 had no effect on IL-6 production and gene expression. 4 Expression of a dominant-negative mutant form of JNK1 that blocked FCS-induced JNK activity had no effect on protein production and gene expression of these cytokines. 5 These findings demonstrate that both ERK and p38 MAPK are involved in FCS-induced LIF secretion, whereas only p38 MAPK is important for IL-6 secretion, and that FCS-induced activation of JNK has no effect on the production of LIF and IL-6. We conclude that, in spite of their similar biological effects, they are differentially regulated at the level of MAPK activity in bone marrow stromal cells.
- Subjects
HEMATOPOIETIC agents; BONE marrow; CYTOKINES; INTERLEUKIN-6
- Publication
British Journal of Pharmacology, 2002, Vol 136, Issue 7, p975
- ISSN
0007-1188
- Publication type
Article
- DOI
10.1038/sj.bjp.0704797