Evidence map›Paper›PMID 40810765›Full record

ArticlePharmacological reports : PR2025

Pretreatment with alendronate augments lipid A-induced IFN-β production via upregulation of cGAS expression.

Satoru Watanabe, Yusuke Kiyoura, Riyoko Tamai

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Article in Pharmacological reports : PR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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3 authors.

Satoru WatanabeDepartment of Infectious Diseases, Ohu University Graduate School of Dentistry, 31-1 Misumido, Tomitamachi, Koriyama, Fukushima, 963-8041, Japan.
Yusuke KiyouraDepartment of Infectious Diseases, Ohu University Graduate School of Dentistry, 31-1 Misumido, Tomitamachi, Koriyama, Fukushima, 963-8041, Japan.
Riyoko TamaiDepartment of Infectious Diseases, Ohu University Graduate School of Dentistry, 31-1 Misumido, Tomitamachi, Koriyama, Fukushima, 963-8041, Japan. r-tamai@den.ohu-u.ac.jp.ORCID http://orcid.org/0000-0002-2782-2763

Funding

a Grant-in-Aid for Scientific Research from the Ohu University School of Dentistry, including the President's discretionary expense 2024-13Japan Society for the Promotion of Science 25K13320
6 · The paper itself

Abstract

backgroundAlendronate (ALN), a nitrogen-containing bisphosphonate (NBP), augments proinflammatory cytokine production by mouse macrophage-like cells incubated with ligands of Toll-like receptor (TLR) 2 and TLR4. The present study investigated whether ALN augments the production of interferon (IFN)-β, which has anti-viral activity.

methodsMouse macrophage-like J774.1 cells were pretreated with or without ALN and then incubated with or without lipid A, a TLR4 ligand. Levels of secreted mouse IFN-β were measured by enzyme-linked immunosorbent assay (ELISA). Expression of interferon regulatory factor (IRF)-5, cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING), retinoic acid-inducible gene-I (RIG-I), downstream of kinase (DOK) 3, caspase-11, Nur77, laminB1, and β-actin was analyzed by Western blot analysis. Cell viability was evaluated by measuring the reduction of 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) to formazan by living cells.

resultsPretreatment with ALN significantly augmented lipid A-induced IFN-β production and nuclear IRF-5 expression in J774.1 cells. In addition, treatment with ALN upregulated the expression of cGAS, RIG-I, and DOK3. Pretreatment of J774.1 cells with RU.521, a cGAS inhibitor, inhibited ALN-augmented IFN-β production, IRF-5 activation, and caspase-11 expression. Similar results were shown in the pretreatment of cells with another inhibitor, G140. RIG012, a RIG-I antagonist, also suppressed ALN-augmented lipid A-induced IFN-β production. Furthermore, pretreatment with ALN significantly upregulated lipid A-induced Nur77 expression, which was also inhibited by RU.521.

conclusionThese results suggest that pretreatment with ALN augments lipid A-induced IFN-β production by J774.1 cells via the upregulation of cGAS expression.

Indexed as

AlendronateInterferon-betaLipid ANucleotidyltransferasesAnimalsCell LineCell SurvivalCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseMacrophagesMiceUp-RegulationAlendronatecGAS protein, mouseCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseInterferon-betaLipid ANucleotidyltransferasesAlendronatecGASInterferon-βLPS receptorNitrogen-containing bisphosphonates

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.