In:
PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 12 ( 2022-12-15), p. e0279134-
Abstract:
Interleukin-6 (IL-6) is a pro-inflammatory and bone-resorptive cytokine that also regulates bone formation. We previously showed that prostaglandin E 1 (PGE 1 ) induces the synthesis of IL-6 by activating p44/p42 mitogen-activated protein kinase (MAPK), stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and p38 MAPK in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether heat shock protein 70 (HSP70), a molecular chaperone that coordinates protein folding and homeostasis, affects PGE 1 -stimulated IL-6 synthesis in MC3T3-E1 cells through the MAPK activation. The osteoblast-like MC3T3-E1 cells were treated with HSP70 inhibitors—VER-155008 and YM-08—, PD98059, SB203580 or SP600125 and then stimulated with PGE 1 . IL-6 synthesis was evaluated using an IL-6 enzyme-linked immunosorbent assay kit. IL-6 mRNA expression was measured by real-time RT-PCR. The phosphorylation of p38 MAPK was evaluated by Western blotting. We found that VER-155008, an HSP70 inhibitor, enhanced the PGE 1 -stimulated IL-6 release and IL-6 mRNA expression. YM-08, another HSP70 inhibitor, also enhanced PGE 1 -stimulated IL-6 release. PD98059, a p44/p42 MAPK inhibitor, and SP600125, a SAPK/JNK inhibitor, upregulated PGE 1 -stimulated IL-6 release. On the other hand, SB203580, a p38 MAPK inhibitor, suppressed PGE 1 -stimulated IL-6 release. YM-08 stimulated the PGE 1 -induced phosphorylation of p38 MAPK. SB203580 suppressed the amplification by YM-08 of the PGE 1 -stimulated IL-6 release. Our results suggest that HSP70 inhibitors upregulate the PGE 1 -stimulated IL-6 synthesis through p38 MAPK in osteoblasts and therefore affect bone remodeling.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0279134
DOI:
10.1371/journal.pone.0279134.g001
DOI:
10.1371/journal.pone.0279134.g002
DOI:
10.1371/journal.pone.0279134.g003
DOI:
10.1371/journal.pone.0279134.g004
DOI:
10.1371/journal.pone.0279134.g005
DOI:
10.1371/journal.pone.0279134.t001
DOI:
10.1371/journal.pone.0279134.s001
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2267670-3
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