Incretins amplify TNF-α-stimulated IL-6 synthesis in osteoblasts: Suppression of the IκB/NF-κB pathway

  • Authors:
    • Kazuhiko Fujita
    • Haruhiko Tokuda
    • Naohiro Yamamoto
    • Shingo Kainuma
    • Tetsu Kawabata
    • Go Sakai
    • Gen Kuroyanagi
    • Rie Matsushima‑Nishiwaki
    • Atsushi Harada
    • Osamu Kozawa
    • Takanobu Otsuka
  • View Affiliations

  • Published online on: February 15, 2017     https://doi.org/10.3892/ijmm.2017.2892
  • Pages: 1053-1060
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Incretins including glucagon-like peptide-1 (GLP-1) and glucose‑dependent insulinotropic polypeptide (GIP) secreted from the small intestine after oral food ingestion are currently recognized to stimulate insulin secretion from pancreatic β cells. We previously reported that p70 S6 kinase limits the tumor necrosis factor‑α (TNF‑α)‑stimulated interleukin-6 (IL‑6) synthesis in osteoblast‑like MC3T3‑E1 cells. In the present study, we investigated the effects of incretins on the TNF‑α‑induced IL‑6 synthesis and the underlying mechanism in MC3T3‑E1 cells. GLP‑1 and GIP significantly upregulated both TNF‑α‑stimulated IL‑6 release and mRNA levels. Wedelolactone, an inhibitor of IκB kinase, amplified the TNF-α-induced IL‑6 release. GLP‑1 significantly attenuated the TNF‑α‑induced phosphorylation of IκB without affecting the phosphorylation of p70 S6 kinase. On the other hand, GLP‑1 markedly induced the phosphorylation of cAMP response element-binding protein (CREB). H‑89, an inhibitor of protein kinase A, significantly suppressed the enhancement by GLP-1 of TNF-α-stimulated IL‑6 release. Dibutyryl cAMP, a permeable analogue of cAMP, which suppressed the TNF-α-induced IκB phosphorylation, amplified the IL‑6 release. These results strongly suggest that incretins upregulate the TNF-α-stimulated IL‑6 synthesis in osteoblasts, and that the amplifying effect of incretin is exerted via reducing the IκB/NF‑κB pathway through the adenylyl cyclase-cAMP system.
View Figures
View References

Related Articles

Journal Cover

April-2017
Volume 39 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Fujita K, Tokuda H, Yamamoto N, Kainuma S, Kawabata T, Sakai G, Kuroyanagi G, Matsushima‑Nishiwaki R, Harada A, Kozawa O, Kozawa O, et al: Incretins amplify TNF-α-stimulated IL-6 synthesis in osteoblasts: Suppression of the IκB/NF-κB pathway. Int J Mol Med 39: 1053-1060, 2017
APA
Fujita, K., Tokuda, H., Yamamoto, N., Kainuma, S., Kawabata, T., Sakai, G. ... Otsuka, T. (2017). Incretins amplify TNF-α-stimulated IL-6 synthesis in osteoblasts: Suppression of the IκB/NF-κB pathway. International Journal of Molecular Medicine, 39, 1053-1060. https://doi.org/10.3892/ijmm.2017.2892
MLA
Fujita, K., Tokuda, H., Yamamoto, N., Kainuma, S., Kawabata, T., Sakai, G., Kuroyanagi, G., Matsushima‑Nishiwaki, R., Harada, A., Kozawa, O., Otsuka, T."Incretins amplify TNF-α-stimulated IL-6 synthesis in osteoblasts: Suppression of the IκB/NF-κB pathway". International Journal of Molecular Medicine 39.4 (2017): 1053-1060.
Chicago
Fujita, K., Tokuda, H., Yamamoto, N., Kainuma, S., Kawabata, T., Sakai, G., Kuroyanagi, G., Matsushima‑Nishiwaki, R., Harada, A., Kozawa, O., Otsuka, T."Incretins amplify TNF-α-stimulated IL-6 synthesis in osteoblasts: Suppression of the IκB/NF-κB pathway". International Journal of Molecular Medicine 39, no. 4 (2017): 1053-1060. https://doi.org/10.3892/ijmm.2017.2892