Alendronate augments lipid A-induced IL-1[beta] release by ASC-deficient RAW264 cells via AP-1 activation

Alendronate (ALN) is an anti-bone-resorptive drug with inflammatory side effects. ALN upregulates lipid A-induced interleukin (IL)-1[alpha] and IL-1[beta] release by J774.1 cells via apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) activation. The present study e...

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Bibliographic Details
Published in:Experimental and therapeutic medicine 2023-12, Vol.26 (6)
Main Authors: Watanabe, Noriyuki, Tamai, Riyoko, Kiyoura, Yusuke
Format: Article
Language:English
Subjects:
Alendronate
Bacterial infections
Bones
Complications and side effects
Development and progression
Health aspects
Interleukin-1
Lipopolysaccharides
Necrosis
Physiological aspects
Prevention
Risk factors
Transcription factors
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Summary:Alendronate (ALN) is an anti-bone-resorptive drug with inflammatory side effects. ALN upregulates lipid A-induced interleukin (IL)-1[alpha] and IL-1[beta] 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-1[beta] 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-1[beta] release. Notably, ALN upregulated the activation of FosB, c-Jun or JunD, but not c-Fos or NF-[kappa]B 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-1[beta] 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-1[beta] release and cell membrane damage in ASC-deficient RAW264 cells via activation of AP-1, but not NF-[kappa]B. Key words: nitrogen-containing bisphosphonate, alendronate, apoptosis-associated speck-like protein containing a caspase recruitment domain, activator protein 1, interleukin-1[beta]
ISSN:1792-0981
DOI:10.3892/etm.2023.12276