ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2013
Rifampin inhibits Toll-like receptor 4 signaling by targeting myeloid differentiation protein 2 and attenuates neuropathic pain.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 75 citations in OpenAlex.
- Rifampin as a novel trigger of drug-induced enterocolitis syndrome.IJTLD open · 2026Article
- Glial cell crosstalk in Parkinson's disease: Mechanisms, implications, and therapeutic strategies.Fundamental research · 2025Review
- Is Rifampin (Rifampicin) Essential for the Treatment of Rhodococcus equi Infections in Foals? A Critical Review of the Role of Rifampin.Journal of veterinary pharmacology and therapeutics · 2025Review
- Andrographolide inhibits the activation of spinal microglia and ameliorates mechanical allodynia.Metabolic brain disease · 2024Article
- Revolutionizing control strategies against Mycobacterium tuberculosis infection through selected targeting of lipid metabolism.Cellular and molecular life sciences : CMLS · 2023Review
- Pharmaceutical Development of Nanostructured Vesicular Hydrogel Formulations of Rifampicin for Wound Healing.International journal of molecular sciences · 2022Article
- Delamanid suppresses CXCL10 expressionFrontiers in immunology · 2022Article
- Neuronal toll like receptor 9 contributes to complete Freund's adjuvant-induced inflammatory pain in mice.Frontiers in molecular neuroscience · 2022Article
- Pentamidine Alleviates Inflammation and Lipopolysaccharide-Induced Sepsis by Inhibiting TLR4 ActivationFrontiers in pharmacology · 2022Article
- Activation of the Hippocampal LXRβ Improves Sleep-Deprived Cognitive Impairment by Inhibiting Neuroinflammation.Molecular neurobiology · 2021Article
- Heme Causes Pain in Sickle MiceAntioxidants & redox signaling · 2021Article
- Paeonol ameliorates CFA-induced inflammatory pain by inhibiting HMGB1/TLR4/NF-κB p65 pathway.Metabolic brain disease · 2021Article
- Bioorthogonal Correlative Light-Electron Microscopy ofACS central science · 2020Article
- Potential Roles of Myeloid Differentiation Factor 2 on Neuroinflammation and Its Possible Interventions.Molecular neurobiology · 2020Review
- The antibiotic bedaquiline activates host macrophage innate immune resistance to bacterial infection.eLife · 2020Article
- Clindamycin inhibits nociceptive response by reducing tumor necrosis factor-α and CXCL-1 production and activating opioidergic mechanisms.Inflammopharmacology · 2020Article
- Stereochemistry and innate immune recognition: (+)-norbinaltorphimine targets myeloid differentiation protein 2 and inhibits toll-like receptor 4 signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- CSF levels of apolipoprotein C1 and autotaxin found to associate with neuropathic pain and fibromyalgia.Journal of pain research · 2019Article
- DREADDed microglia in pain: Implications for spinal inflammatory signaling in male rats.Experimental neurology · 2018Article
- Dissecting the Innate Immune Recognition of Opioid Inactive Isomer (+)-Naltrexone Derived Toll-like Receptor 4 (TLR4) Antagonists.Journal of chemical information and modeling · 2018Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Rifampin has been used for the treatment of bacterial infections for many years. Clinically, rifampin has been found to possess immunomodulatory effects. However, the molecular target responsible for the immunosuppressive effects of rifampin is not known. Herein, we show that rifampin binds to myeloid differentiation protein 2 (MD-2), the key coreceptor for innate immune TLR4. Rifampin blocked TLR4 signaling induced by LPS, including NF-κB activation and the overproduction of proinflammatory mediators nitric oxide, interleukin 1β, and tumor necrosis factor α in mouse microglia BV-2 cells and macrophage RAW 264.7 cells. Rifampin's inhibition of TLR4 signaling was also observed in immunocompetent rat primary macrophage, microglia, and astrocytes. Further, we show that rifampin (75 or 100 mg/kg b.i.d. for 3 d, intraperitoneal) suppressed allodynia induced by chronic constriction injury of the sciatic nerve and suppressed nerve injury-induced activation of microglia. Our findings indicate that MD-2 is a important target of rifampin in its inhibition of innate immune function and contributes to its clinically observed immune-suppressive effect. The results also suggest that rifampin may be repositioned as an agent for the treatment of neuropathic pain.
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Registered trials
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.