Diurnal rhythm and pathogens induced expression of toll-like receptor 9 (TLR9) in Pelteobagrus vachellii

Qin, Chuanjie; Sun, Jiaxian; Yang, He; Wang, Jun; Han, Yongwang; Li, Huatao; Liao, Xufeng

doi:10.1016/j.fsi.2019.02.038

Cited by 13 publications

(8 citation statements)

References 34 publications

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“…A large number of studies have found that TLR9 is activated in the immune cells of the body after stimulation by various viral infections, and it then exerts its immune function by stimulating the immune system. [ 18 , 20 ] TLR9 has the ability to identify HBV and initiate an immune response. TLR9 expressed in cells is primarily located in the endoplasmic reticulum.…”

Section: Discussionmentioning

confidence: 99%

H3K9 acetylation modification and TLR9 immune regulation mechanism in patients after anti-HBV treatment

Zhu

Wang

et al. 2022

Medicine

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To improve the curative effect of anti-hepatitis B virus (HBV) drugs, methods such as thymosin and entecavir combination have become a focus of clinical investigation. The aim of this retrospective experimental study was to explore the potential mechanism of action of thymosin a1 (Ta1) combined with entecavir in the treatment of HBV infection. A total of 28 patients with chronic hepatitis B, 29 patients treated with thymosin a1 and entecavir combination, and 15 healthy individuals were enrolled in this study. RT-qPCR was conducted to evaluate the mRNA levels of TLR9 in peripheral blood mononuclear cells (PBMCs). The serum level of TLR9 protein was analyzed by ELISA. The binding of TLR9 gene to the protein H3K9Ac in PBMCs was assessed by chromatin immunoprecipitation, and serum inflammatory factors were detected by Luminex technology. The expression levels of TLR9 mRNA and serum TLR9 protein in patients with HBV infection were significantly lower than those in subjects in the control group before treatment but increased after treatment with the Ta1 and entecavir combination. Moreover, the acetylation protein H3K9Ac was significantly bound to the promoter region of the TLR9 gene in patients with HBV infection treated with the Ta1 and entecavir combination compared to that in patients with HBV infection without treatment. Furthermore, the expression levels of interleukin 6 (IL-6), interleukin 12 (IL-12), interferon gamma, and necrosis factor alpha in patients with HBV infection after the combination treatment were slightly decreased compared to those in patients with HBV infection without treatment. In conclusion, the histone acetylation modification of TLR9 was significantly improved in patients with HBV infection after treatment with the Ta1 and entecavir combination, which elevated the expression of TLR9 at the mRNA and protein levels and further regulated the expression of IL-6, IL-12, and other cytokines.

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Section: Discussionmentioning

confidence: 99%

H3K9 acetylation modification and TLR9 immune regulation mechanism in patients after anti-HBV treatment

Zhu

Wang

et al. 2022

Medicine

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“…A large number of literature reports have found that TLR9 is activated in the immune cells of the body after stimulation by various viral infections and exerts its immune function by stimulating the immune system (18-19). TLR9 has the ability to identify HBV virus and initiate immune response.…”

Section: Discussionmentioning

confidence: 99%

“…Toll-like receptors (TLRs) are an important class of receptors that recognize foreign microorganisms in innate immunity, which can initiate direct killing effect of innate immunity and mediate secondary onset of adaptive immunity (16)(17). TLR9 is one of the receptors with multiple effects and big influence (18). Ta1 can improve the body's anti-infective ability by activating TLR signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

“…Clinical studies have found that treatment of patients with chronic hepatitis B by entecavir and thymosin a1 has significantly better efficacy in overall than entecavir alone, indicating that strengthening immune regulation during antiviral therapy can further strengthen hepatitis B virus clearance effect, and better improve patients' clinical symptoms, enhance body immunity and curative effect. For this reason, exploring the molecular mechanism of entecavir and thymosin a1 in the treatment of chronic hepatitis B will provide an important theoretical reference for the proposal of more treatment schemes.A large number of literature reports have found that TLR9 is activated in the immune cells of the body after stimulation by various viral infections and exerts its immune function by stimulating the immune system(18)(19). TLR9 has the ability to identify HBV virus and initiate immune response.…”

mentioning

confidence: 99%

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Study on H3K9 acetylation modification and TLR9 immune regulation mechanism in patients with anti-HBV treatment using thymosin a1 combined with entecavir

Zhu

Wang

et al. 2020

Preprint

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For hepatitis B antiviral treatment, there has been no comprehensive method yet. Interferon has poor antiviral efficacy, while nucleoside drugs have long course of treatment and high relapse rate. To improve the anti-HBV curative effect, treatment methods such as thymosin combined with entecavir have become a focus of clinical investigation. To explore potential mechanism of the combination therapy, based on previous studies, this paper explores the relationship between TLR9 expression in PBMCs, secretion of corresponding downstream inflammatory factors and HBV load in anti-HBV treatment with Thymosin a1 (Ta1) combined with entecavir. Chromatin immunoprecipitation combined with PCR method was adopted to detect H3K9 acetylation modification in patients. The relationship between TLR9 expression was explored using RT-QPCR, the relationship between secretion of inflammatory factors, efficacy and TLR9 mRNA expression was determined using Luminex technology. The results showed that during anti-HBV treatment with Ta1 combined with entecavir, histone acetylation increased in patients' PBMCs, acetylated protein H3K9Ac had significant binding with promoter region of the TRL9 gene, thereby increasing the expression of TRL9 mRNA, activating the immune pathway under TRL9 regulation, promoting secretion of inflammation factors IL-6, IL-12, IFN-γ, and TNF-α, boosting the progress of antiviral therapy. H3K9 acetylation modification of TLR9 exists and plays an important role in patients with chronic hepatitis B. During the combination therapy with entecavir and Ta1, histone acetylation modification of TLR9 was significantly improved, which increased the expression of TLR9 at the mRNA and protein levels, and further regulated IL-6, IL-12 and other cytokines.

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“…The newly produced TLR9 is retained in the endoplasmic reticulum and trafficked to endocytic vesicles mediated by UNC-93B, a 12-membrane-spanning protein, for sensing microbial CpG DNAs [12] . Until now, fish TLR9 has been cloned and characterized in puffer fish (Takifugu rubripes) [13] , zebrafish (Danio rerio) [14] , gilthead seabream (Sparus aurata) [15] , Japanese flounder (Paralichthys olivaceus) [16] , large yellow croaker (Pseudosciaena crocea) [17] , rainbow trout (Oncorhynchus mykiss), [18] , silver pomfret (Pampus argenteus) [19] , spiny eel (Mastacembelus armatus) [20] and darkbarbel catfish (Pelteobagrus vachellii) [21] .…”

Section: Introductionmentioning

confidence: 99%

Molecular Characterization and Expression Analysis of Toll-like Receptor 9 Gene in Turbot, Scophthalmus Maximus

Wang¹,

Li²,

Liu³

et al. 2020

JCMR

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Toll-like receptors (TLRs) have emerged as key sensors of invading microbes by recognizing pathogen-associated molecular patterns and activating innate immune responses. TLR9 functions as a pattern-recognition receptor that recognizes unmethylated CpG motifs in bacterial and viral DNA. In this study, the full cDNA and genomic sequences of tlr9 in Scophthalmus maximus (smtlr9) were identified and characterized. The full-length cDNA of smtlr9 was of 3754 bp encoding a polypeptide of 1066 amino acid residues. The genome sequence of smtlr9 was composed of 4083 nucleotides, including three exons and two introns. The putative Smtlr9 protein was characterized by a signal peptide sequence, a leucine-rich repeat domain (LRD) containing 15 leucine-rich repeats (LRRs), a transmembrane region, and a Toll/interleukin-1 receptor (TIR) domain. The putative protein shows the highest sequence identity (36.0~73.6%) to human and fish TLR9s. Phylogenetic analysis grouped Smtlr9 with other teleost Tlr9s. The smtlr9 mRNA was constitutively expressed in all tissues examined, with the highest level in the head kidney and kidney. The smtlr9 transcription level was up-regulated by ODN2395 in the muscle, head kidney, spleen, and gills.

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Diurnal rhythm and pathogens induced expression of toll-like receptor 9 (TLR9) in Pelteobagrus vachellii

Cited by 13 publications

References 34 publications

H3K9 acetylation modification and TLR9 immune regulation mechanism in patients after anti-HBV treatment

H3K9 acetylation modification and TLR9 immune regulation mechanism in patients after anti-HBV treatment

Study on H3K9 acetylation modification and TLR9 immune regulation mechanism in patients with anti-HBV treatment using thymosin a1 combined with entecavir

Molecular Characterization and Expression Analysis of Toll-like Receptor 9 Gene in Turbot, Scophthalmus Maximus

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