ArticlePloS one2015
Botulinum neurotoxin type A induces TLR2-mediated inflammatory responses in macrophages.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A Meta-Analysis of the Efficacy and Safety of Botulinum Toxin Type A for the Management of Scars After Facial Surgery.Journal of cosmetic dermatology · 2025Pooled it
- Trial
- Itaconate modifications: Mechanisms and applications.Journal of intensive medicine · 2026Review
- Pro-Inflammatory Signaling in Dermal Fibroblasts: A Possible Role of Different Botulinum Toxin Formulations on IL-6 Expression.Journal of cosmetic dermatology · 2026Article
- Therapeutic Modulation of the Nox2-Hv1-ROS Axis by Botulinum Neurotoxin A Confers Protection Against CoClInternational journal of molecular sciences · 2025Article
- Article
- Pioneering pain management with botulinum toxin type A: From anti-inflammation to regenerative therapies.Heliyon · 2025Review
- Review
- Botulinum neurotoxin serotype A inhibited ocular angiogenesis through modulating glial activation via SOCS3.Angiogenesis · 2024Article
- Complexing Protein-Free Botulinum Neurotoxin A Formulations: Implications of Excipients for Immunogenicity.Toxins · 2024Review
- Metabolite itaconate in host immunoregulation and defense.Cellular & molecular biology letters · 2023Review
- Botulinum neurotoxin A ameliorates depressive-like behavior in a reserpine-induced Parkinson's disease mouse model via suppressing hippocampal microglial engulfment and neuroinflammation.Acta pharmacologica Sinica · 2023Article
- The signaling pathways and therapeutic potential of itaconate to alleviate inflammation and oxidative stress in inflammatory diseases.Redox biology · 2022Review
- Review
- The molecular mechanism of GADD153 in apoptosis of keloid fibroblasts exposed to botulinum toxin type A.Journal of cellular and molecular medicine · 2021Article
- Neurotrophic effects of Botulinum neurotoxin type A in hippocampal neurons involve activation of Rac1 by the non-catalytic heavy chain (HCIBRO neuroscience reports · 2021Article
- Unilateral facial injection of Botulinum neurotoxin A attenuates bilateral trigeminal neuropathic pain and anxiety-like behaviors through inhibition of TLR2-mediated neuroinflammation in mice.The journal of headache and pain · 2021Article
- NF-κB signalling as a pharmacological target in COVID-19: potential roles for IKKβ inhibitors.Naunyn-Schmiedeberg's archives of pharmacology · 2021Review
- Botulinum Neurotoxin Therapy for Depression: Therapeutic Mechanisms and Future Perspective.Frontiers in psychiatry · 2021Review
- Dramatic neurological and biological effects by botulinum neurotoxin type A on SH-SY5Y neuroblastoma cells, beyond the blockade of neurotransmitter release.BMC pharmacology & toxicology · 2020Article
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Botulinum neurotoxin type A (BoNT/A) is the most potent protein toxin and causes fatal flaccid muscle paralysis by blocking neurotransmission. Application of BoNT/A has been extended to the fields of therapeutics and biodefense. Nevertheless, the global response of host immune cells to authentic BoNT/A has not been reported. Employing microarray analysis, we performed global transcriptional profiling of RAW264.7 cells, a murine alveolar macrophage cell line. We identified 70 genes that were modulated following 1 nM BoNT/A treatment. The altered genes were mainly involved in signal transduction, immunity and defense, protein metabolism and modification, neuronal activities, intracellular protein trafficking, and muscle contraction. Microarray data were validated with real-time RT-PCR for seven selected genes including tlr2, tnf, inos, ccl4, slpi, stx11, and irg1. Proinflammatory mediators such as nitric oxide (NO) and tumor necrosis factor alpha (TNFα) were induced in a dose-dependent manner in BoNT/A-stimulated RAW264.7 cells. Increased expression of these factors was inhibited by monoclonal anti-Toll-like receptor 2 (TLR2) and inhibitors specific to intracellular proteins such as c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 mitogen-activated protein kinase (MAPK). BoNT/A also suppressed lipopolysaccharide-induced NO and TNFα production from RAW264.7 macrophages at the transcription level by blocking activation of JNK, ERK, and p38 MAPK. As confirmed by TLR2-/- knock out experiments, these results suggest that BoNT/A induces global gene expression changes in host immune cells and that host responses to BoNT/A proceed through a TLR2-dependent pathway, which is modulated by JNK, ERK, and p38 MAPK.
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