Retraction of: Immunoregulatory Role of MicroRNA-21 in Macrophages in Response to Bacillus Calmette- Guerin Infection Involves Modulation of the TLR4/MyD88 Signaling Pathway

Background/Aims: The purpose of this study is to explore the immunoregulatory role of microRNA-21 (miR-21) targeting of the TLR4/MyD88 signaling pathway in macrophages in response to Bacillus Calmette-Guerin (BCG) infection. Methods: After infection with BCG, mouse RAW246.7 cells were assigned into control, BCG, miR-21 mimic + BCG, mimic-negative control (NC) + BCG, miR-21 inhibitor + BCG, inhibitor-NC + BCG, BCG + TAK242 (an inhibitor of the TLR4 signaling pathway), and miR-21 inhibitor + TAK242 + BCG groups. Western blotting and qRT-PCR were used to detect the expression of miR-21, TLR4 and MyD88. The levels of TNF-a, IL-6 and IL-10 were detected by enzyme-linked immunosorbent assay (ELISA). Cell viability was measured using an MTT assay. Cell apoptosis and necrosis rates were detected using flow cytometry. Results: Compared with the control group, miR-21 expression and levels of TNF-a, IL-6 and IL-10, as well as cell apoptosis and necrosis rates, were elevated, while expression of TLR4 and MyD88, as well as cell viability, were reduced in BCG infection groups. Compared with the BCG group, miR-21 expression was increased in the miR-21 mimic + BCG group but decreased in the miR-21 inhibitor + BCG and miR-21 inhibitor + TAK242 + BCG groups. The expression of TLR4 and MyD88, as well as the cell viability, were decreased, while levels of TNF-a, IL-6 and IL-10, as well as cell apoptosis and necrosis rates, were increased in the miR-21 mimic + BCG and TAK242 + BCG groups. The opposite trends were found in the miR-21 inhibitor + BCG group. Compared with the TAK242 + BCG group, the miR-21 inhibitor + TAK242 + BCG group had higher expression of TLR4 and MyD88 as well as higher cell viability and lower levels of TNF-a, IL-6, IL-10, cell apoptosis and necrosis rates. However, the miR-21 inhibitor + TAK242 + BCG group exhibited the opposite trends when compared with the miR-21 inhibitor + BCG group. Conclusion: Our results suggest that miR-21 can negatively modulate the TLR4/MyD88 signaling pathway, resulting in decreased cell viability, increased cell apoptosis and increased levels of inflammatory factors following BCG infection in macrophages.

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Role of the CXCR3‑mediated TLRs/MyD88 signaling pathway in promoting the development of hepatitis B into cirrhosis and liver cancer

Molecular Medicine Reports ◽

10.3892/mmr.2021.12378 ◽

2021 ◽

Vol 24 (4) ◽

Author(s):

Gang Yuan ◽

Bin Chen ◽

Yina Meng ◽

Jialin Lu ◽

Xiaojun Shi ◽

...

Keyword(s):

Liver Cancer ◽

Hepatitis B ◽

Signaling Pathway ◽

Myd88 Signaling

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406. Role of MyD88 Signaling Pathway in the Host Immune Responses in Adenoviral Vector-Mediated Gene Therapy

Molecular Therapy ◽

10.1016/j.ymthe.2005.06.409 ◽

2005 ◽

Vol 11 ◽

pp. S157

Keyword(s):

Gene Therapy ◽

Immune Responses ◽

Signaling Pathway ◽

Adenoviral Vector ◽

Host Immune Responses ◽

Myd88 Signaling

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

Journal of Neuroinflammation ◽

10.1186/s12974-020-02066-y ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Wenliang Su ◽

Huan Cui ◽

Danning Wu ◽

Jiawen Yu ◽

Lulu Ma ◽

...

Keyword(s):

Signaling Pathway ◽

High Mobility ◽

Adaptor Protein ◽

Immunofluorescent Staining ◽

Inhibitory Peptide ◽

Tlr4 Signaling ◽

Innate Immunity Pathway ◽

Myd88 Signaling ◽

Myeloid Differentiation Factor

Abstract Background As a classic innate immunity pathway, Toll-like receptor 4 (TLR4) signaling has been intensively investigated for its function of pathogen recognition. The receptor is located not only on immune cells but also on sensory neurons and spinal glia. Recent studies revealed the involvement of neuronal TLR4 in different types of pain. However, the specific role of TLR4 signaling in the pain symptom of endometriosis (EM) remains obscure. Methods The rat endometriosis model was established by transplanting uterine horn tissue into gastrocnemius. Western blotting and/or immunofluorescent staining were applied to detect high mobility group box 1 (HMGB1), TLR4, myeloid differentiation factor-88 adaptor protein (MyD88), and nuclear factor kappa-B-p65 (NF-κB-p65) expression, as well as the activation of astrocyte and microglia. The antagonist of TLR4 (LPS-RS-Ultra, LRU) and MyD88 homodimerization inhibitory peptide (MIP) were intrathecally administrated to assess the behavioral effects of blocking TLR4 signaling on endometriosis-related pain. Results Mechanical hyperalgesia was observed at the graft site, while HMGB1 was upregulated in the implanted uterine tissue, dorsal root ganglion (DRG), and spinal dorsal horn (SDH). Compared with sham group, upregulated TLR4, MyD88, and phosphorylated NF-κB-p65 were detected in the DRG and SDH in EM rats. The activation of astrocytes and microglia in the SDH was also confirmed in EM rats. Intrathecal application of LRU and MIP alleviated mechanical pain on the graft site of EM rats, with decreased phosphorylation of NF-κB-p65 in the DRG and reduced activation of glia in the SDH. Conclusions HMGB1-TLR4-MyD88 signaling pathway in the DRG and SDH may involve in endometriosis-related hyperpathia. Blockade of TLR4 and MyD88 might serve as a potential treatment for pain in endometriosis.

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519. Unique Role of the TLR9-MyD88 Signaling Pathway in Dendritic Cells in AAV Capsid-Specific CD8+ T Cell Activation

Molecular Therapy ◽

10.1016/s1525-0016(16)34128-4 ◽

2015 ◽

Vol 23 ◽

pp. S208 ◽

Cited By ~ 1

Author(s):

Geoffrey L. Rogers ◽

Irene Zolotukhin ◽

Roland W. Herzog

Keyword(s):

Dendritic Cells ◽

T Cell ◽

Signaling Pathway ◽

T Cell Activation ◽

Cell Activation ◽

Cd8 T Cell ◽

Unique Role ◽

Myd88 Signaling

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TLR3-Dependent Activation of TLR2 Endogenous Ligands via the MyD88 Signaling Pathway Augments the Innate Immune Response

Cells ◽

10.3390/cells9081910 ◽

2020 ◽

Vol 9 (8) ◽

pp. 1910

Author(s):

Hellen S. Teixeira ◽

Jiawei Zhao ◽

Ethan Kazmierski ◽

Denis F. Kinane ◽

Manjunatha R. Benakanakere

Keyword(s):

Signaling Pathway ◽

Innate Immune ◽

Poly I:C ◽

Innate Immune Responses ◽

Endogenous Ligands ◽

Polyinosinic:Polycytidylic Acid ◽

Tlr3 Signaling ◽

Myd88 Signaling

The role of the adaptor molecule MyD88 is thought to be independent of Toll-like receptor 3 (TLR3) signaling. In this report, we demonstrate a previously unknown role of MyD88 in TLR3 signaling in inducing endogenous ligands of TLR2 to elicit innate immune responses. Of the various TLR ligands examined, the TLR3-specific ligand polyinosinic:polycytidylic acid (poly I:C), significantly induced TNF production and the upregulation of other TLR transcripts, in particular, TLR2. Accordingly, TLR3 stimulation also led to a significant upregulation of endogenous TLR2 ligands mainly, HMGB1 and Hsp60. By contrast, the silencing of TLR3 significantly downregulated MyD88 and TLR2 gene expression and pro-inflammatory IL1β, TNF, and IL8 secretion. The silencing of MyD88 similarly led to the downregulation of TLR2, IL1β, TNF and IL8, thus suggesting MyD88 to somehow act downstream of TLR3. Corroborating in vitro data, Myd88−/− knockout mice downregulated TNF, CXCL1; and phospho-p65 and phospho-IRF3 nuclear localization, upon poly I:C treatment in a mouse model of skin infection. Taken together, we identified a previously unknown role for MyD88 in the TLR3 signaling pathway, underlying the importance of TLRs and adapter protein interplay in modulating endogenous TLR ligands culminating in pro-inflammatory cytokine regulation.

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