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Induction of interleukin-6 expression by bone morphogenetic protein-6 in macrophages requires both SMAD and p38 signaling pathways.


ABSTRACT: Unlike the prototype transforming growth factor-? (TGF-?), bone morphogenetic protein-6 (BMP-6) activates macrophages. Here, we report that BMP-6 induces the expression of IL-6 in macrophages. Using overexpression and knockdown experiments, we demonstrate that BMP receptor type II and activin-like kinase-2 are necessary for IL-6 induction by BMP-6. At the intracellular level, both Smad and p38 signaling pathways are required for the induction of IL-6. The cross-talk between the two pathways occurs at the level of transcription factor GATA4 and Smad 1/4. These results, taken together, demonstrate a novel BMP-6 signaling mechanism in which both the Smad and non-Smad pathways directly interact to activate the transcription of a target gene.

SUBMITTER: Lee GT 

PROVIDER: S-EPMC2998138 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Induction of interleukin-6 expression by bone morphogenetic protein-6 in macrophages requires both SMAD and p38 signaling pathways.

Lee Geun Taek GT   Kwon Seok Joo SJ   Lee Jae-Ho JH   Jeon Seong Soo SS   Jang Kee Taek KT   Choi Han Yong HY   Lee Hyun Moo HM   Kim Wun-Jae WJ   Kim Seong Jin SJ   Kim Isaac Yi IY  

The Journal of biological chemistry 20101001 50


Unlike the prototype transforming growth factor-β (TGF-β), bone morphogenetic protein-6 (BMP-6) activates macrophages. Here, we report that BMP-6 induces the expression of IL-6 in macrophages. Using overexpression and knockdown experiments, we demonstrate that BMP receptor type II and activin-like kinase-2 are necessary for IL-6 induction by BMP-6. At the intracellular level, both Smad and p38 signaling pathways are required for the induction of IL-6. The cross-talk between the two pathways occu  ...[more]

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