Suppression of TLR4-MyD88 signaling pathway attenuated chronic mechanical pain in a rat model of endometriosis

Su, Wenliang; Cui, Huan; Wu, Dong; Yu, Jiawen; Ma, Lulu; Xiu-hua, Zhang; Huang, Yuguang

doi:10.1186/s12974-020-02066-y

Cited by 30 publications

(16 citation statements)

References 43 publications

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“…Therefore, we speculated that the inhibition role of MS19 on HMGB1 secretion is partially mediated through NF-κB signaling and TNF-α-dependent mechanism, since that ODN exhibited a strong inhibition against the NF-κB activation and TNF-α production in this study. In addition, after its release, extracellular HMGB1 usually acts as a DAMP molecule and transmits signals to the cell interior via the activation of receptors including TLR4, resulting in the formation of a positive feedback loop that potentially amplifies local inflammatory responses ( Su et al, 2021 ; Teo Hansen Selno et al, 2021 ). Thus, MS19 might also interact with the secreted HMGB1, leading to the functional inactivation by the induction of a conformational change.…”

Section: Discussionmentioning

confidence: 99%

A microsatellite DNA-derived oligodeoxynucleotide attenuates lipopolysaccharide-induced acute lung injury in mice by inhibiting the HMGB1-TLR4-NF-κB signaling pathway

Zhang

Wang

et al. 2022

Front. Microbiol.

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Acute lung injury (ALI) with uncontrolled inflammatory response has high morbidity and mortality rates in critically ill patients. Pathogen-associated molecular patterns (PAMPs) are involved in the development of uncontrolled inflammatory response injury and associated lethality. In this study, we investigated the inhibit effect of MS19, a microsatellite DNA-derived oligodeoxynucleotide (ODN) with AAAG repeats, on the inflammatory response induced by various PAMPs in vitro and in vivo. In parallel, a microsatellite DNA with AAAC repeats, named as MS19-C, was used as controls. We found that MS19 extensively inhibited the expression of inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α induced by various PAMPs stimulation, including DNA viruses, RNA viruses, bacterial components lipopolysaccharide (LPS), and curdlan, as well as the dsDNA and dsRNA mimics, in primed bone marrow-derived macrophage (BMDM). Other than various PAMPs, MS19 also demonstrated obvious effects on blocking the high mobility group box1 (HMGB1), a representative damage-associated-molecular pattern (DAMP), nuclear translocation and secretion. With the base substitution from G to C, MS19-C has been proved that it has lost the inhibitory effect. The inhibition is associated with nuclear factor kappa B (NF-κB) signaling but not the mitogen-activated protein kinase (MAPK) transduction. Moreover, MS19 capable of inhibiting the IL-6 and TNF-α production and blocking the HMGB1 nuclear translocation and secretion in LPS-stimulated cells was used to treat mice ALI induced by LPS in vivo. In the ALI mice model, MS19 significantly inhibited the weight loss and displayed the dramatic effect on lessening the ALI by reducing consolidation, hemorrhage, intra-alveolar edema in lungs of the mice. Meanwhile, MS19 could increase the survival rate of ALI by downregulating the inflammation cytokines HMGB1, TNF-a, and IL-6 production in the bronchoalveolar lavage fluid (BALF). The data suggest that MS19 might display its therapeutic role on ALI by inhibiting the HMGB1-TLR4-NF-κB signaling pathway.

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Section: Discussionmentioning

confidence: 99%

A microsatellite DNA-derived oligodeoxynucleotide attenuates lipopolysaccharide-induced acute lung injury in mice by inhibiting the HMGB1-TLR4-NF-κB signaling pathway

Zhang

Wang

et al. 2022

Front. Microbiol.

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“…The method of quantification for immunofluorescence staining referred to previous studies. 29 , 30 Briefly, two non-adjacent spinal cord sections were randomly selected from the spinal cord segment (L3–L5) of each rat, and three rats were selected for each group. The intensity of GFAP and IBA1 staining was measured with Image J.…”

Section: Methodsmentioning

confidence: 99%

Astrocyte-microglia interaction through C3/C3aR pathway modulates neuropathic pain in rats model of chronic constriction injury

Mou

Zhu³

et al. 2022

Mol Pain

Self Cite

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Neuropathic pain (NP) is the cardinal symptom of neural injury, and its underlying molecular mechanism needs further investigation. Complements, especially complement 3 (C3), are involved in the pathophysiology of many neurological disorders, while the specific role of C3 in NP is still obscure. In this study, we found that both C3 and its receptor C3aR were upregulated in the spinal dorsal horn in a rat chronic constriction injury (CCI) model. In addition, C3 was mainly detected in astrocytes, while C3aR was expressed in microglia and neuron. Intrathecal injection of C3 antibody and C3aR antagonist alleviated NP in CCI model together with reduced M1 polarization of microglia. Our finding suggested that blockade of the C3/C3aR pathway might be a novel strategy for NP.

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“…Extracellular high mobility group box-1 (HMGB-1), a prototypical molecule of damage-associated molecular patterns, activates NF-κB in endometriotic cells by binding to its receptor, Toll-like receptor 4 (TLR4), and induces inflammatory responses in the environment of endometriosis with sustained oxidative stress [52,53]. In addition, the HMGB-1/TLR4/NF-κB axis can also induce the proliferation and invasion of endometriotic cells and contribute to endometriosis-induced pain [52][53][54]. During retrograde menstruation, erythrocytes are carried into the pelvic cavity of patients with endometriosis, and the lysis of erythrocytes results in iron release, with free iron serving as a source of ROS [55].…”

Section: Oxidative Stressmentioning

confidence: 99%

“…In an SD rat model of endometriosis, NF-κB overexpression was found in the DRG and spinal dorsal horn (SDH), which was induced by the HMGB-1/TLR4/MyD88 pathway and contributed to mechanical hyperalgesia at the graft site of ectopic endometrium 54 . Inhibiting the expression of TLR4 or MyD88 could decrease NF-κB p65 phosphorylation in the DRG, alleviating chronic endometriosis-induced pain 54 .…”

Section: Role Of Nf-κb In Endometriosis Pathogenesismentioning

confidence: 99%

An Update on the Multifaceted Role of NF-kappaB in Endometriosis

2022

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Endometriosis remains a common but challenging gynecological disease among reproductive-aged women with an unclear pathogenesis and limited therapeutic options. Numerous pieces of evidence suggest that NF-κB signaling, a major regulator of inflammatory responses, is overactive in endometriotic lesions and contributes to the onset, progression, and recurrence of endometriosis. Several factors, such as estrogen, progesterone, oxidative stress, and noncoding RNAs, can regulate NF-κB signaling in endometriosis. In the present review, we discuss the mechanisms by which these factors regulate NF-κB during endometriosis progression and provide an update on the role of NF-κB in affecting endometriotic cells, peritoneal macrophages (PMs) as well as endometriosis-related symptoms, such as pain and infertility. Furthermore, the preclinical drugs for blocking NF-κB signaling in endometriosis are summarized, including plant-derived medicines, NF-κB inhibitors, other known drugs, and the potential anti-NF-κB drugs predicted through the Drug-Gene Interaction Database. The present review discusses most of the studies concerning the multifaceted role of NF-κB signaling in endometriosis and provides a summary of NF-κB-targeted treatment in detail.

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Suppression of TLR4-MyD88 signaling pathway attenuated chronic mechanical pain in a rat model of endometriosis

Cited by 30 publications

References 43 publications

A microsatellite DNA-derived oligodeoxynucleotide attenuates lipopolysaccharide-induced acute lung injury in mice by inhibiting the HMGB1-TLR4-NF-κB signaling pathway

A microsatellite DNA-derived oligodeoxynucleotide attenuates lipopolysaccharide-induced acute lung injury in mice by inhibiting the HMGB1-TLR4-NF-κB signaling pathway

Astrocyte-microglia interaction through C3/C3aR pathway modulates neuropathic pain in rats model of chronic constriction injury

An Update on the Multifaceted Role of NF-kappaB in Endometriosis

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