The role of dendritic cells regulated by HMGB1/TLR4 signalling pathway in myocardial ischaemia reperfusion injury

Xue, Jiyang; Ge, Hanwei; Lin, Zhiyong; Wang, Hanlei; Lin, Wei; Liu, Yong; Wu, Guowei; Xia, Jie; Zhao, Qifeng

doi:10.1111/jcmm.14192

Cited by 27 publications

(24 citation statements)

References 59 publications

(122 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Firstly, HMGB1 is a chemoattractant for immature DCs (111). HMGB1, specifically the B box motif, stimulates DCs to mature via TLR4 signaling (111–113). This has been shown by the presence of co-stimulatory surface molecules CD80, CD86, and HLA-A, -B, -C, as well as various other marker molecules that demonstrate maturation of DCs (111).…”

Section: Hmgb1 and Cancermentioning

confidence: 99%

Johnny on the Spot-Chronic Inflammation Is Driven by HMGB1

et al. 2019

View full text Add to dashboard Cite

Although much has been made of the role of HMGB1 acting as an acute damage associated molecular pattern (DAMP) molecule, prompting the response to tissue damage or injury, it is also released at sites of chronic inflammation including sites of infection, autoimmunity, and cancer. As such, the biology is distinguished from homeostasis and acute inflammation by the recruitment and persistence of myeloid derived suppressor cells, T regulatory cells, fibrosis and/or exuberant angiogenesis depending on the antecedents and the other individual inflammatory partners that HMGB1 binds and focuses, including IL-1β, CXCL12/SDF1, LPS, DNA, RNA, and sRAGE. High levels of HMGB1 released into the extracellular milieu and its persistence in the microenvironment can contribute to the pathogenesis of many if not all autoimmune disorders and is a key factor that drives inflammation further and worsens symptoms. HMGB1 is also pivotal in the maintenance of chronic inflammation and a “wound healing” type of immune response that ultimately contributes to the onset of carcinogenesis and tumor progression. Exosomes carrying HMGB1 and other instructive molecules are released and shape the response of various cells in the chronic inflammatory environment. Understanding the defining roles of REDOX, DAMPs and PAMPs, and the host response in chronic inflammation requires an alternative means for positing HMGB1's central role in limiting and focusing inflammation, distinguishing chronic from acute inflammation.

show abstract

Section: Hmgb1 and Cancermentioning

confidence: 99%

Johnny on the Spot-Chronic Inflammation Is Driven by HMGB1

et al. 2019

View full text Add to dashboard Cite

show abstract

“…TLR4-mediated signal transduction is activated during the process of MIRI (29,30). Notably, Zhang et al (12) identified that the inflammation-associated transcription factor DEC1 regulated the cellular responses in P. gingivalis infection by promoting the production of IL-1β and TNF-α through the activation of TLR4.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of DEC1 by RNA interference attenuates ischemia/reperfusion‑induced myocardial inflammation by inhibiting the TLR4/NF‑κB signaling pathway

Wang

Zhang

et al. 2020

Exp Ther Med

View full text Add to dashboard Cite

Inflammation has been implicated in the pathogenesis of myocardial ischemia/reperfusion (I/R) injury (MIRI). Previous studies have confirmed that deleted in esophageal cancer 1 (DEC1) is an important transcription factor in inflammation. However, the role of DEC1 in MIRI remains unclear. The present study aimed to determine whether the downregulation of DEC1 by RNA interference alleviated inflammation to protect against MIRI. Adult Sprague-Dawley rats (n=48) were randomly divided into four groups: Sham; I/R; adenovirus expressing green fluorescent protein control (Ad-G-Control); and DEC1-targeting RNA interference (Ad-G-DEC1) groups. Following gene delivery 4 days later, the rat myocardial I/R model was established and myocardial enzymes [creatine kinase (CK) and lactate dehydrogenase (LDH)] were detected. Hematoxylin and eosin (H&E) staining was performed to evaluate the myocardial damage and the infarct area was assessed using Evans Blue/triphenyltetrazolium chloride staining. The inflammatory mediators interleukin (IL)-β and tumor necrosis factor (TNF)-α were also detected using ELISA kits to assess the inflammatory response. Finally, western blotting and reverse transcription-quantitative PCR were used to analyze the expression levels of associated proteins and mRNAs. Ad-G-DEC1 RNA interference markedly decreased DEC1 expression levels. In addition, following the downregulation of DEC1 expression, the infarct size, CK, LDH, Toll-like receptor (TLR)4, NF-κB, IL-β and TNF-α levels were all significantly decreased. In conclusion, the results of the present study suggested that the downregulation of DEC1 may decrease the inflammation by suppressing the TLR4/NF-κB signaling pathway, which may represent a therapeutic target for MIRI.

show abstract

“…Ethyl pyruvate improves lupus symptoms by regulating the HMGB1-TLR4 pathway, thereby alleviating the inflammatory microenvironment and delaying the aging of bone marrow mesenchymal stem cells 27. TLR4 is a necessary receptor in the proinflammatory process of HMGB1, and NF-кB is downstream of the TLR4 signaling pathway 28…”

Section: Discussionmentioning

confidence: 99%

<p>Co-Delivery Of Dihydroartemisinin And HMGB1 siRNA By TAT-Modified Cationic Liposomes Through The TLR4 Signaling Pathway For Treatment Of Lupus Nephritis</p>

Diao¹,

Jin²,

Wang³

et al. 2019

IJN

View full text Add to dashboard Cite

Background and purposeSystemic lupus erythematous (SLE) is an autoimmune disease caused by many factors. Lupus nephritis (LN) is a common complication of SLE and represents a major cause of morbidity and mortality. Previous studies have shown the advantages of multi-targeted therapy for LN and that TLR4 signaling is a target of anti-LN drugs. High-mobility group box 1 (HMGB1), a nuclear protein with a proinflammatory cytokine activity, binds specifically to TLR4 to induce inflammation. We aimed to develop PEGylated TAT peptide-cationic liposomes (TAT-CLs) to deliver anti-HMGB1 siRNA and dihydroartemisinin (DHA) to increase LN therapeutic efficiency and explore their treatment mechanism.MethodsWe constructed the TAT-CLs-DHA/siRNA delivery system using the thin film hydration method. The uptake and localization of Cy3-labeled siRNA were detected by confocal microscopy and flow cytometry. MTT assays were used to detect glomerular mesangial cell proliferation. Real-time PCR, Western blot analysis, and ELISA evaluated the anti-inflammatory mechanism of TAT-CLs-DHA/siRNA.ResultsWe constructed the TAT-CLs-DHA/siRNA delivery system measuring approximately 140 nm with superior storage and serum stabilities. In vitro, it showed significantly greater uptake compared with unmodified liposomes and significant inhibition of glomerular mesangial cell proliferation. TAT-CLs-DHA/siRNA inhibited NF-κB activation in a concentration-dependent manner. Real-time PCR and Western blot analysis showed that TAT-CLs-DHA/siRNA downregulated expression of HMGB1 mRNA and protein. TAT-CLs-DHA/siRNA markedly diminished Toll-like receptor 4 (TLR4) expression and subsequent activation of MyD88, IRAK4, and NF-κB.ConclusionTAT-CLs-DHA/siRNA may have the potential for treatment of inflammatory diseases such as LN mediated by the TLR4 signaling pathway.

show abstract

The role of dendritic cells regulated by HMGB1/TLR4 signalling pathway in myocardial ischaemia reperfusion injury

Cited by 27 publications

References 59 publications

Johnny on the Spot-Chronic Inflammation Is Driven by HMGB1

Johnny on the Spot-Chronic Inflammation Is Driven by HMGB1

Downregulation of DEC1 by RNA interference attenuates ischemia/reperfusion‑induced myocardial inflammation by inhibiting the TLR4/NF‑κB signaling pathway

<p>Co-Delivery Of Dihydroartemisinin And HMGB1 siRNA By TAT-Modified Cationic Liposomes Through The TLR4 Signaling Pathway For Treatment Of Lupus Nephritis</p>

Contact Info

Product

Resources

About