TLR9 expression

ZL targeted let-7i to inhibit TLR9 expression, thereby inhibiting the activation of the TLR9/MyD88 pathway, promoting the M2 polarization, and inhibiting the development of inflammation in AIS.

In clinical lymphoma samples, the expression of METTL3, YTHDF1 and TLR9 was highly correlated with immune cells infiltration. This study reveals a novel mechanism that EBV represses the important innate immunity molecule TLR9 through modulating the host m6A modification system.

P2, N=10, Recruiting, University of Arizona | Trial primary completion date: Mar 2024 --> Mar 2025

To conclude, our results demonstrate the TLR2 and TLR9-specific intrabody-mediated signaling pathway inhibition of autoregulatory inflammation inside cancer cells and their proliferation, resulting in the suppression of pancreatic tumor cell growth. These findings underscore the potential of specific intrabody-mediated TLR inhibition in the ER relevant for tumor growth inhibition and open up a new therapeutic intervention strategy for the treatment of pancreatic cancer.

A septic mouse model was established by cecal ligation and puncture (CLP), then administered with lentivirus encoding si-TLR9/LY294002...TLR9 expression was augmented in the cecal tissues, TLR9 and MyD88 interaction was enhanced, nuclear p65 protein level was increased, cytoplasmic p65 protein level was decreased, and the nuclear factor kappa B (NF-κB) pathway was activated in CLP-induced septic mice, while TLR9 knockout protected against CLP-induced sepsis via the MyD88/NF-κB pathway inactivation. Briefly, TLR9 inhibition-mediated protection against CLP-induced sepsis was associated with a reduction in pro-inflammatory cytokine release and a promotion of bacterial clearance via a mechanism involving the MyD88/NF-κB pathway inactivation.

Moreover, future challenges in the establishment of CpG delivery systems for immunotherapeutic applications are discussed. We expect that the continuously growing interest in the development of CpG-based immunotherapy will certainly fuel the excitement and stimulation in medicine research.

To obviate the need for a second drug formulation and reduce the risk of toxicity, we exploited the multivalent nature of this targeting platform to co-deliver the TAP siRNA and a DC maturation agent, a CpG containing oligonucleotide, to cDC1 in vivo and show that it was more effective than Clec9a targeting of TAP siRNA in combination with CD40 antibody. This study describes a way to manipulate the function of cDC1 cells in vivo using a broadly applicable antibody-based targeting platform to deliver multiple biological agents to specific cells in vivo to potentiate (immune) therapy and to probe the biology of specific cell types in their natural settings.

Our findings demonstrate that EBV promotes the production of inflammatory cytokines IL-1β and TNF-α and chemokines IL-8 and MCP-1 in HGFs through the TLR9/MyD88/NF-κB pathway.

Acupuncture pretreatment can alleviate exercise-induced skeletal muscle damage, which may be related to modulating the expression of TLR9/MyD88/NF-κB signaling pathway to inhibit the inflammatory response.

No abstract available

Additionally, in vivo experiments further verified that TLR9 promoted tumour growth and immune escape by inhibiting PARP1. Collectively, TLR9 activation induced immunosuppression and tumorigenesis via PARP1/PD-L1 signaling pathway in OSCC, providing important insights for subsequent in-depth exploration of the mechanism of OSCC.

In conclusion, the role of HPV in OC and OPC is minor, and p16 constitutes a poor biomarker for HPV positivity in Kerala, India. Intracellular TLRs are correlated with the degree of inflammation in OPC but not in OC and may potentially constitute a medical target in the therapy of HNC in the future.

Cervicovaginal microbiota dysbiosis might lead to the CpG motif increased, which was closely associated with TLR9 high expression, and ultimately might promote the progression of cervical lesions.

Our study indicated that TFAM regulate irradiated cardiomyocytes pyroptosis through mtDNA/TLR9/NF-kB pathway. We provide a novel mechanism of RIMD, revealing an underappreciated intervention target for RIMD.

Soluble toll-like receptors 4 and sTLR9 are over-expressed in patients with metastatic and non-metastatic BC than in benign cases. The expression levels of sTLR4 and TLR9 have clinical interest as indicators of tumor aggressiveness suggested to be prognostic biomarkers. Toll-like receptors may represent therapeutic targets in breast cancer.

Our results provided information on TLRs expression and potential regulatory networks in LUAD. Moreover, our results suggested TLR2/7/8 as a potential prognostic biomarker for lung adenocarcinoma.

Mechanistically, we revealed that NETs could interact with TLR9 to decrease Merlin phosphorylation which contributed to TNBC cell ferroptosis resistance. Our work provides a novel insight into the mechanism of NETs promoting TNBC progression and blocking the key modulator of NETs might be a promising therapeutic strategy in TNBC.

Co-expression analysis of CD180/MD-1 at the transcriptional level has revealed potential novel signaling partners for this TLR complex, providing rationale for further phenotypic and functional studies in CLL. Since CD180 can rewire IgM-mediated signaling to a pro-apoptotic pathway in CLL [8], it will be important to determine if CD180/MD-1 has synergistic or antagonistic effects on the signaling partners proposed here. The high correlation between CD180/MD-1 and TLR10 and SLAMF6 mRNA suggest these receptors as rational starting points for such studies.

In the presence of the BTK-inhibitor ibrutinib, we found a subset of previously non-responsive NR/RR samples became ‘sensitised’ to TLR9 activation, showing an increase in CLL cell migration in response to stimulation with ODN 2006... In a cohort of 74 primary CLL samples, a dichotomous migratory response was observed in response to the TLR9 agonist ODN 2006. 53% showed an increase in CLL cell migration (categorised as ‘Responders’[R]), whilst 47% showed either no change or a decrease (categorised as ‘Non/ Reverse Responders’[NR/RR]). There was a significant (but not exclusive), correlation with mutational status, with 71 vs.

There is an increased pDC in the TME of smokers' lung cancer, and the response of pDC to DNA damaging treatment would lead a conducive environment to ICIs containing regimens. These findings suggest that R&D that induces an increase in the activated pDC population is continuously required to enhance therapeutic effectiveness of ICIs-containing therapies in lung cancer.

In support of our computational findings, the validation of key results using polymerase chain reaction and other experimental methods is warranted in the Indian population. In general, this study might be able to delineate the guideline for identifying the most damaging SNPs and enhances the understating of the risk factors for cancer and disease susceptibilities.

CONCLUSIONS : Subjects carrying the C/C genotype are more likely to develop complications from H. pylori infection due to greater activation of TLR9-IFNα signaling. The “C” allele is more prevalent in AAm than in Caucasians, suggesting a higher risk in this racial minority.

A significant increase in TLR9 expression was observed in or around lung cancer immediately after ionizing radiation or cisplatin treatment in LSL-Kras G12D mouse model... pDC is an innate immune cell population that showed a prominent increase in smokers’ TME compared to that of non-smokers, suggesting that its increase may be one the factors that smokers’ lung cancer show favorable responses to ICI than that of non-smokers. These findings suggest that the pDC signature can be developed as a biomarker predicting the response to ICIs and increasing the number of pDCs or its activity may improve treatment outcome of ICIs.

We conclude that MDS HSPCs are primed for inflammasome activation via ox-mtDNA released by pyroptotic cells. Blocking the TLR9/ox-mtDNA axis may prove to be a novel therapeutic strategy for MDS.

TLR9 is not only a prognostic biomarker but also a potential target for B-ALL therapy. CpG 685 monotherapy might be applicable to Ph B-ALL patients with C-MYC overexpression and without BAX deletion. CpG 685 may also serve as an effective combinational therapy against Ph B-ALL.

It seems that royal jelly has anti-viral and anti-inflammatory roles in the in vivo conditions in a dependent manner in TLR3, TLR2, and TLR8. Therefore, it can be suggested as a safe complementary agent for patients with hepatitis B.

Moreover, the nuclear factor kappa B (NF-κB) signaling pathway was activated by TLR9, and TLR9-induced malignant phenotype of OS cells was abrogated by the NF-κB antagonist BAY11-7082. Our study indicated that TLR9 might play a critical role in facilitating OS progression by activating the NF-κB signaling pathway, which may provide a valuable therapeutic target for OS.

Localized targeting was confirmed in vivo by labeling CpG-Den with IR800 revealing specific accumulation in the mice BM. Our data supports TLR9-targeting potential in a proof-of-concept strategy to selectively target primary MDS malignant cells to restore and enhance hematopoiesis while avoiding toxicities.

TLR9-increased expression was associated with HPV persistence in previous studies; hence, bacterial coinfections may enhance this risk. Prospective measurements of type III IFNs and IFNLR1 are warranted to evaluate whether this response may act as a double-edged sword in infected epithelia.

Cytoplasmic TLR3, TLR7, TLR8 and TLR9 were not associated with 5-year survival. In conclusion, high nuclear TLR3 expression seems to have prognostic impact in gastric cancer, while TLR7, TLR8 and TLR9 do not.

These results indicate that HPV may affect breast cancer TLR9 expression and thereby breast cancer prognosis, through treatment responses. Although HPV was not detected in the small pilot set of our clinical samples, this issue needs to be further studied in larger data sets.

The ERK inhibitor decreased the CsEVs-induced IL-6 and TNF-α secretion. The present study elucidated for the first time that CsEVs induced IL-6 and TNF-α production in BECs via the TLR9-mediated ERK pathway.

The follow-up time to recurrence in advanced stage was statistically lower than early stage (p= 0.007). Overexpression of TLRs 2, 9 play role in the pathogenesis and tumor development of OSCC and can be applied as biomarker in prognostic approaches.

Our data reveal that TLR9 promotes the initiating stages of GC and facilitates Helicobacter-induced gastric inflammation and hyperplasia, thus providing in vivo evidence for TLR9 as a candidate therapeutic target in GC.