Alendronate augments lipid A‑induced IL‑1β release by ASC‑deficient RAW264 cells via AP‑1 activation

  • Authors:
    • Noriyuki Watanabe
    • Riyoko Tamai
    • Yusuke Kiyoura
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  • Published online on: October 26, 2023     https://doi.org/10.3892/etm.2023.12276
  • Article Number: 577
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Abstract

Alendronate (ALN) is an anti‑bone‑resorptive drug with inflammatory side effects. ALN upregulates lipid A‑induced interleukin (IL)‑1α and IL‑1β release by J774.1 cells via apoptosis‑associated speck‑like protein containing a caspase recruitment domain (ASC) activation. The present study examined whether ALN augmented lipid A‑induced proinflammatory cytokine production using ASC‑deficient mouse macrophage‑like RAW264 cells. Pretreatment of RAW264 cells with ALN significantly augmented lipid A‑induced IL‑1β release, although ALN did not upregulate the expression of Toll‑like receptor 4, myeloid differentiation factor 88 (MyD88) and caspase‑11. Moreover, pretreatment of caspase‑11‑deficient RAW264.7 cells with ALN significantly augmented lipid A‑induced IL‑1β release. Notably, ALN upregulated the activation of FosB, c‑Jun or JunD, but not c‑Fos or NF‑κB in RAW264 cells. Furthermore, pretreatment with the activator protein 1 (AP‑1) inhibitor SR11302, but not the c‑Fos inhibitor T‑5224, before addition of ALN inhibited ALN‑augmented IL‑1β release by lipid A‑treated RAW264 cells. SR11302 also reduced ALN‑augmented lactate dehydrogenase release by the cells. These findings collectively suggested that ALN augmented lipid A‑induced IL‑1β release and cell membrane damage in ASC‑deficient RAW264 cells via activation of AP‑1, but not NF‑κB.
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December-2023
Volume 26 Issue 6

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Watanabe N, Tamai R and Kiyoura Y: Alendronate augments lipid A‑induced IL‑1β release by ASC‑deficient RAW264 cells via AP‑1 activation. Exp Ther Med 26: 577, 2023
APA
Watanabe, N., Tamai, R., & Kiyoura, Y. (2023). Alendronate augments lipid A‑induced IL‑1β release by ASC‑deficient RAW264 cells via AP‑1 activation. Experimental and Therapeutic Medicine, 26, 577. https://doi.org/10.3892/etm.2023.12276
MLA
Watanabe, N., Tamai, R., Kiyoura, Y."Alendronate augments lipid A‑induced IL‑1β release by ASC‑deficient RAW264 cells via AP‑1 activation". Experimental and Therapeutic Medicine 26.6 (2023): 577.
Chicago
Watanabe, N., Tamai, R., Kiyoura, Y."Alendronate augments lipid A‑induced IL‑1β release by ASC‑deficient RAW264 cells via AP‑1 activation". Experimental and Therapeutic Medicine 26, no. 6 (2023): 577. https://doi.org/10.3892/etm.2023.12276