Toll-like receptor 2 plays an essential role in electroacupuncture analgesia in a mouse model of inflammatory pain

Background: Inflammatory pain occurs when local tissue injury activates macrophages and neutrophils, hence increasing pro-inflammatory cytokine and chemokine levels. Toll-like receptor 2 (TLR2) antagonism reportedly suppresses neuropathic and inflammatory pain. Aims: In the present study, we investigated the effect of electroacupuncture (EA) on TLR2 and related signalling molecules in a complete Freund’s adjuvant (CFA)-induced mouse model of inflammatory pain to determine whether EA can attenuate inflammatory pain via the TLR2 signalling pathway. Methods: EA significantly reduced mechanical and thermal hyperalgesia in the animal model. A similar effect was produced by TLR2 antagonism induced by CU-CPT22 injection. Results: TLR2 expression in the dorsal root ganglia, spinal cord and thalamus increased following induction of inflammation. Expression levels of downstream molecules such as pPI3K, pAkt and pmTOR also increased, as did those of MAPK subfamily members such as pERK, pp38 and pJNK. Transcription factors (pCREB and pNFκB) and nociceptive ion channels (Nav1.7 and Nav1.8) were also involved. Conclusion: Increased expression of the above molecules was attenuated by both EA and TLR2 antagonism. Our results show that EA attenuates inflammatory pain via TLR2 signalling.

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Toll-Like Receptor 2-Mediated Glial Cell Activation in a Mouse Model of Cuprizone-Induced Demyelination

Molecular Neurobiology ◽

10.1007/s12035-017-0838-2 ◽

2017 ◽

Vol 55 (8) ◽

pp. 6237-6249 ◽

Cited By ~ 15

Author(s):

Stefan Esser ◽

Larissa Göpfrich ◽

Kai Bihler ◽

Eugenia Kress ◽

Stella Nyamoya ◽

...

Keyword(s):

Mouse Model ◽

Glial Cell ◽

Cell Activation ◽

Toll Like Receptor ◽

Glial Cell Activation ◽

Toll Like Receptor 2

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Toll-Like Receptor 2 Expression as a New Hallmark of Advanced Endometriosis

Cells ◽

10.3390/cells9081813 ◽

2020 ◽

Vol 9 (8) ◽

pp. 1813 ◽

Cited By ~ 1

Author(s):

Małgorzata Sobstyl ◽

Paulina Niedźwiedzka-Rystwej ◽

Ewelina Grywalska ◽

Izabela Korona-Głowniak ◽

Anna Sobstyl ◽

...

Keyword(s):

Dendritic Cells ◽

B Lymphocytes ◽

Characteristic Curve ◽

Cost Effective ◽

Peripheral Blood Lymphocytes ◽

Toll Like Receptor ◽

Myeloid Dendritic Cells ◽

Tlr2 Expression ◽

Toll Like Receptor 2 ◽

Effective Diagnosis

Recent evidence suggests that immunological aspects play a pivotal role in this disorder. Toll-like receptor 2 (TLR2) is crucial in recognizing microbial infections and mediating innate immune response. The objective of our study was to rate with flow cytometry the levels of several subsets of dendritic cells, monocytes, and basic peripheral blood lymphocytes expressing TLR2, aiming at the determination of a possible correlation between the expression of TLR2 and the clinical outcomes of endometriosis in 40 patients and 40 age-matched healthy women. Our study showed the importance of TLR2 expression, mainly on myeloid dendritic cells (mDCs) and B cells in patients with endometriosis. Both mDCs BDCA1+CD19-TLR2+ and B lymphocytes CD19+TLR-2+ proved useful in the differentiation of affected individuals with stages 3–4 of the disease (area under the receiver operating characteristic curve /AUC/ = 0.96, p < 0.0001 for mDCs; AUC = 0.78, p = 0.0001 for B lymphocytes), and those presenting adhesion (AUC = 0.92, p < 0.0001 for mDCs; AUC = 0.82, p < 0.0001 for B lymphocytes) or infertility (AUC = 0.83, p < 0.0001 for mDCs; AUC = 0.73, p = 0.006 for B lymphocytes). Our findings suggest that the levels of TLR2-expressing cells, particularly mDCs and B lymphocytes, may be an effective biomarker of endometriosis, because the disease currently lacks clinically useful noninvasive biomarkers enabling early and cost-effective diagnosis.

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Electroacupuncture Reduces Carrageenan- and CFA-Induced Inflammatory Pain Accompanied by Changing the Expression of Nav1.7 and Nav1.8, rather than Nav1.9, in Mice Dorsal Root Ganglia

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/312184 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 11

Author(s):

Chun-Ping Huang ◽

Hsiang-Ni Chen ◽

Hong-Lin Su ◽

Ching-Liang Hsieh ◽

Wei-Hsin Chen ◽

...

Keyword(s):

Sodium Channels ◽

Dorsal Root Ganglia ◽

Inflammatory Pain ◽

Dorsal Root ◽

Low Frequency ◽

Thermal Hyperalgesia ◽

Nerve Fibers ◽

Drg Neurons ◽

Plantar Surface ◽

Voltage Gated Sodium Channels

Several voltage-gated sodium channels (Navs) from nociceptive nerve fibers have been identified as important effectors in pain signaling. The objective of this study is to investigate the electroacupuncture (EA) analgesia mechanism by changing the expression of Navs in mice dorsal root ganglia (DRG). We injected carrageenan and complete Freund's adjuvant (CFA) into the mice plantar surface of the hind paw to induce inflammation and examined the antinociception effect of EA at the Zusanli (ST36) acupoint at 2 Hz low frequency. Mechanical hyperalgesia was evaluated by using electronic von Frey filaments, and thermal hyperalgesia was assessed using Hargreaves' test. Furthermore, we observed the expression and quality of Navs in DRG neurons. Our results showed that EA reduced mechanical and thermal pain in inflammatory animal model. The expression of Nav1.7 and Nav1.8 was increased after 4 days of carrageenan- and CFA-elicited inflammatory pain and further attenuated by 2 Hz EA stimulation. The attenuation cannot be observed in Nav1.9 sodium channels. We demonstrated that EA at Zusanli (ST36) acupoint at 2 Hz low-frequency stimulation attenuated inflammatory pain accompanied by decreasing the expression of Nav1.7 and 1.8, rather than Nav1.9, sodium channels in peripheral DRG neurons.

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Toll-Like Receptor 2 Contributes to Chemokine Gene Expression and Macrophage Infiltration in the Dorsal Root Ganglia after Peripheral Nerve Injury

Molecular Pain ◽

10.1186/1744-8069-7-74 ◽

2011 ◽

Vol 7 ◽

pp. 1744-8069-7-74 ◽

Cited By ~ 35

Author(s):

Donghoon Kim ◽

Byunghyun You ◽

Hyoungsub Lim ◽

Sung Joong Lee

Keyword(s):

Gene Expression ◽

Peripheral Nerve ◽

Nerve Injury ◽

Dorsal Root Ganglia ◽

Peripheral Nerve Injury ◽

Dorsal Root ◽

Toll Like Receptor ◽

Chemokine Gene ◽

Toll Like Receptor 2 ◽

Chemokine Gene Expression

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Toll-like Receptor 2 as a Marker Molecule of Advanced Ovarian Cancer

Biomolecules ◽

10.3390/biom11081205 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1205

Author(s):

Małgorzata Sobstyl ◽

Paulina Niedźwiedzka-Rystwej ◽

Rafał Hrynkiewicz ◽

Dominika Bębnowska ◽

Izabela Korona-Głowniak ◽

...

Keyword(s):

Ovarian Cancer ◽

Advanced Ovarian Cancer ◽

Screening Tests ◽

Control Group ◽

Newly Diagnosed ◽

Toll Like Receptor ◽

Tlr2 Expression ◽

Diagnostic Approaches ◽

Toll Like Receptor 2 ◽

Marker Molecule

Ovarian cancer is a global problem that affects women of all ages. Due to the lack of effective screening tests and the usually asymptomatic course of the disease in the early stages, the diagnosis is too late, with the result that less than half of the patients diagnosed with ovarian cancer (OC) survive more than five years after their diagnosis. In this study, we examined the expression of TLR2 in the peripheral blood of 50 previously untreated patients with newly diagnosed OC at various stages of the disease using flow cytometry. The studies aimed at demonstrating the usefulness of TLR2 as a biomarker in the advanced stage of ovarian cancer. In this study, we showed that TLR2 expression levels were significantly higher in women with more advanced OC than in women in the control group. Our research sheds light on the prognostic potential of TLR2 in developing new diagnostic approaches and thus in increasing survival in patients with confirmed ovarian cancer.

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Increasing toll-like receptor 2 on astrocytes induced by Schwann cell-derived exosomes promotes recovery by inhibiting CSPGs deposition after spinal cord injury

Journal of Neuroinflammation ◽

10.1186/s12974-021-02215-x ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Dayu Pan ◽

Yongjin Li ◽

Fuhan Yang ◽

Zenghui Lv ◽

Shibo Zhu ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Schwann Cell ◽

Western Blot ◽

Signaling Pathway ◽

Functional Recovery ◽

Toll Like Receptor ◽

Tlr2 Expression ◽

Cord Injury ◽

Toll Like Receptor 2

Abstract Background Traumatic spinal cord injury (SCI) is a severely disabling disease that leads to loss of sensation, motor, and autonomic function. As exosomes have great potential in diagnosis, prognosis, and treatment of SCI because of their ability to easily cross the blood–brain barrier, the function of Schwann cell-derived exosomes (SCDEs) is still largely unknown. Methods A T10 spinal cord contusion was established in adult female mice. SCDEs were injected into the tail veins of mice three times a week for 4 weeks after the induction of SCI, and the control group was injected with PBS. High-resolution transmission electron microscope and western blot were used to characterize the SCDEs. Toll-like receptor 2 (TLR2) expression on astrocytes, chondroitin sulfate proteoglycans (CSPGs) deposition and neurological function recovery were measured in the spinal cord tissues of each group by immunofluorescence staining of TLR2, GFAP, CS56, 5-HT, and β-III-tublin, respectively. TLR2f/f mice were crossed to the GFAP-Cre strain to generate astrocyte specific TLR2 knockout mice (TLR2−/−). Finally, western blot analysis was used to determine the expression of signaling proteins and IKKβ inhibitor SC-514 was used to validate the involved signaling pathway. Results Here, we found that TLR2 increased significantly on astrocytes post-SCI. SCDEs treatment can promote functional recovery and induce the expression of TLR2 on astrocytes accompanied with decreased CSPGs deposition. The specific knockout of TLR2 on astrocytes abolished the decreasing CSPGs deposition and neurological functional recovery post-SCI. In addition, the signaling pathway of NF-κB/PI3K involved in the TLR2 activation was validated by western blot. Furthermore, IKKβ inhibitor SC-514 was also used to validate this signaling pathway. Conclusion Thus, our results uncovered that SCDEs can promote functional recovery of mice post-SCI by decreasing the CSPGs deposition via increasing the TLR2 expression on astrocytes through NF-κB/PI3K signaling pathway.

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Loss of Toll-like receptor 2 results in accelerated leukemogenesis in the NUP98-HOXD13 mouse model of MDS

Blood ◽

10.1182/blood-2017-08-801944 ◽

2018 ◽

Vol 131 (9) ◽

pp. 1032-1035 ◽

Cited By ~ 4

Author(s):

Darlene A. Monlish ◽

Sima T. Bhatt ◽

Eric J. Duncavage ◽

Zev J. Greenberg ◽

John L. Keller ◽

...

Keyword(s):

Mouse Model ◽

Toll Like Receptor ◽

Toll Like Receptor 2

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Toll-Like Receptor 2 Agonist Pam3CSK4 Alleviates the Pathology of Leptospirosis in Hamster

Infection and Immunity ◽

10.1128/iai.00708-16 ◽

2016 ◽

Vol 84 (12) ◽

pp. 3350-3357 ◽

Cited By ~ 13

Author(s):

Wenlong Zhang ◽

Naisheng Zhang ◽

Xufeng Xie ◽

Jian Guo ◽

Xuemin Jin ◽

...

Keyword(s):

Tissue Injury ◽

Interleukin 10 ◽

Peritoneal Macrophages ◽

High Ratio ◽

Toll Like Receptor ◽

Wild Type ◽

Necrosis Factor Alpha ◽

Content Type ◽

Target Organs ◽

Toll Like Receptor 2

Leptospirosis, caused by pathogenic spirochetes, is a zoonotic disease of global importance. The detailed pathogenesis of leptospirosis is still unclear, which limits the ideal treatment of leptospirosis. In this study, we analyzed the expression of Toll-like receptor 2 (TLR2) and TLR4 in target organs of both resistant mice and susceptible hamsters after Leptospira interrogans serovar Autumnalis infection. TLR2 but not TLR4 transcripts in mouse organs contrasted with delayed induction and overexpression in hamster organs. Coinjection of leptospires and the TLR2 agonist Pam3CSK4 into hamsters improved their survival rate, alleviated tissue injury, and decreased the abundance of leptospires in target organs. The production of interleukin-10 (IL-10) from tissues was enhanced in hamsters of the group coinjected with leptospires and Pam3CSK4 compared with the leptospira-injected group. Similarly, IL-10 levels in TLR2-deficient mice were lower than those in wild-type mice. A high ratio of IL-10/tumor necrosis factor alpha (TNF-α) levels was found in both infected wild-type mice and hamsters coinjected with leptospires and Pam3CSK4. Moreover, TLR2-dependent IL-10 expression was detected in peritoneal macrophages after leptospira infection. Our data demonstrate that coinjection of leptospires and Pam3CSK4 alleviates the pathology of leptospirosis in hamsters; this effect may result from the enhanced expression of TLR2-dependent IL-10.

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