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Proinflammatory cytokines, IL-1β and TNF-α, induce expression of interleukin-34 mRNA via JNK- and p44/42 MAPK-NF-κB pathway but not p38 pathway in osteoblasts

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Abstract

The aim of this study is to investigate the induction of interleukin-34 (IL-34) and macrophage colony-stimulating factor (M-CSF) mRNA by inflammatory cytokines and the involvement of mitogen-activated protein kinases (MAPKs) in this signaling pathway in human osteoblasts as both IL-34 and M-CSF bind to the same receptor c-FMS. Among four inflammatory cytokines [(IL-1β, IL-6, IL-17, and tumor necrosis factor-α (TNF-α)], IL-34 mRNA expression level was dramatically induced by IL-1β (17-fold) and TNF-α (74-fold). IL-1β and TNF-α activated the intracellular mitogen-activated protein kinases (MAPKs): p44/42 MAPK, p38, and c-Jun N-terminal kinase (JNK) as well as nuclear factor-κB (NF-κB) in osteoblasts. IL-1β- and TNF-α-mediated induction of IL-34 mRNA expression was decreased by JNK inhibitor. Interestingly, although treatment of MEK-1/2 inhibitor showed no reduction in the increase of IL-34 mRNA expression by cytokines, combination of MEK-1/2 inhibitor and JNK inhibitor significantly inhibited IL-1β- and TNF-α-mediated IL-34 mRNA expression level compared to those by each inhibitor alone. On the other hand, M-CSF mRNA expression level was significantly induced by both IL-1β and TNF-α by up to 7- and 11-fold, respectively. IL-1β- and TNF-α-mediated induction of M-CSF mRNA was not affected by p38, JNK, and MEK-1/2 inhibitors. However, NF-κB inhibitor completely inhibited the elevation of M-CSF mRNA expression by these cytokines. These results showed that proinflammatory cytokines, IL-1β and TNF-α, induced the expression of IL-34 mRNA via JNK and p44/42 MAPK but not p38 in human osteoblasts while p38, JNK, and p44/42 MAPK were not involved in the induction of M-CSF mRNA expression by these cytokines.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Discovery Biology, Global Research and Development, St. Louis Laboratories, Pfizer Inc., 700 Chesterfield Parkway West, mail zone AA3C, Chesterfield, MO, 63017, USA

    Hiroyuki Eda, Hideaki Shimada, David R. Beidler & Joseph B. Monahan

  2. Exploratory Research Laboratories, Research Center, Ajinomoto Pharmaceuticals Co., Ltd., 1-1, Suzuki, Kawasaki-ku, Kawasaki-shi, Kanagawa, 210-8681, Japan

    Hiroyuki Eda

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  1. Hiroyuki Eda
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  2. Hideaki Shimada
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  3. David R. Beidler
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  4. Joseph B. Monahan
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Correspondence to Hiroyuki Eda.

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Eda, H., Shimada, H., Beidler, D.R. et al. Proinflammatory cytokines, IL-1β and TNF-α, induce expression of interleukin-34 mRNA via JNK- and p44/42 MAPK-NF-κB pathway but not p38 pathway in osteoblasts. Rheumatol Int 31, 1525–1530 (2011). https://doi.org/10.1007/s00296-010-1688-7

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  • DOI: https://doi.org/10.1007/s00296-010-1688-7

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