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Role of mitogen‐activated protein kinase family in serum‐induced leukaemia inhibitory factor and interleukin‐6 secretion by bone marrow stromal cells
Author(s) -
Nakao Takafumi,
Kim Shokei,
Ohta Kensuke,
Kawano Hitomi,
Hino Masayuki,
Miura Katsuyuki,
Tatsumi Noriyuki,
Iwao Hiroshi
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704797
Subject(s) - stromal cell , mapk/erk pathway , haematopoiesis , bone marrow , cytokine , secretion , leukemia inhibitory factor , biology , protein kinase a , p38 mitogen activated protein kinases , microbiology and biotechnology , cancer research , kinase , medicine , endocrinology , immunology , stem cell , interleukin 6
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. 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 2 ‐terminal kinase (JNK). 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. 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. 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.British Journal of Pharmacology (2002) 136 , 975–984. doi: 10.1038/sj.bjp.0704797