Irreversible inhibition of RANK expression as a possible mechanism for IL-3 inhibition of RANKL-induced osteoclastogenesis.

Autor: Khapli SM; National Center for Cell Science, University of Pune Campus, Pune 411 007, India., Tomar GB, Barhanpurkar AP, Gupta N, Yogesha SD, Pote ST, Wani MR
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2010 Sep 03; Vol. 399 (4), pp. 688-93. Date of Electronic Publication: 2010 Aug 05.
DOI: 10.1016/j.bbrc.2010.07.143
Abstrakt: IL-3, a cytokine secreted by activated T lymphocytes, stimulates the proliferation, differentiation and survival of pluripotent hematopoietic stem cells. In this study, we investigated the mechanism of inhibitory action of IL-3 on osteoclast differentiation. We show here that IL-3 significantly inhibits receptor activator of NF-kappaB (RANK) ligand (RANKL)-induced activation of c-Jun N-terminal kinase (JNK). IL-3 down-regulates expression of c-Fos and nuclear factor of activated T cells (NFATc1) transcription factors. In addition, IL-3 down-regulates RANK expression posttranscriptionally in both purified osteoclast precursors and whole bone marrow cells. Furthermore, the inhibitory effect of IL-3 on RANK expression was irreversible. Interestingly, IL-3 inhibits in vivo RANK expression in mice. Thus, we provide the first evidence that IL-3 irreversibly inhibits RANK expression that results in inhibition of important signaling molecules induced by RANKL.
(Copyright 2010 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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