Sinomenine regulates CD14/TLR4, JAK2/STAT3 pathway and calcium signal via α7nAChR to inhibit inflammation in LPS-stimulated macrophages

Zhu, Rencheng; Zhi, Yingkun; Lee, Yi; Luo, Jin-Fang; Li, Jing; Bai, Shasha; Liu, Liang; Peixun, Wang; Zhou, Hua; Dong, Yi

doi:10.1080/08923973.2019.1568451

Cited by 38 publications

(20 citation statements)

References 24 publications

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“…Interestingly, the SIN-hyaluronic acid conjugate seemed to be an effective therapeutic means for the treatment of knee osteoarthritis [26]. A recent research also showed SIN could decrease the expression of CD14/TLR4 and intracellular free calcium level, activate JAK2/STAT3 pathway to inhibit inflammatory response through α7nAChR in macrophages [27]. Besides that, SIN has also been widely used in a variety of cancers including prostate cancer [28], esophageal squamous cell carcinoma [29], renal carcinoma [11], and breast cancer [30].…”

Section: Discussionmentioning

confidence: 99%

Sinomenine sensitizes human gastric cancer cells to cisplatin through negative regulation of PI3K/AKT/Wnt signaling pathway

Liu

Tan

et al. 2019

Anti-Cancer Drugs

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Sinomenine (SIN) has been reported its antitumor effects on various types of human cancers, but there is no available information regarding the antitumor effects of SIN and cisplatin on gastric cancer. Here, we examined the antitumor effects of SIN combined with cisplatin on gastric cancer cells as well as the underlying biological mechanisms. CCK-8 assay and Calcusyn 2.0 software analysis, Hoechst 33258 staining and flow cytometry, transwell assay showed that SIN and cisplatin synergistically inhibited growth, induced apoptosis, and suppressed invasion than did either drug alone in gastric cancer cells. Interestingly, no change in the AKT level was found, whereas SIN and cisplatin led to a dramatic decrease in p-AKT level compared with either alone treatment. SIN and cisplatin further decreased the Bcl-2, procaspase-3, and β-catenin, but increased Bax, cleaved dcaspase 3, MMP9, and MMP2 in combined group than in either alone group. Immunofluorescence staining showed again a significant decrease in nucleus β-catenin was found in combined group. These data suggested that SIN sensitizes human gastric cancer cells to cisplatin through negative regulation of PI3K/AKT/Wnt signaling pathway. In conclusion, SIN and cisplatin exerted synergistic antitumor effects in gastric cancer cells and might constitute a promising therapeutic approach for gastric cancer.

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Section: Discussionmentioning

confidence: 99%

Sinomenine sensitizes human gastric cancer cells to cisplatin through negative regulation of PI3K/AKT/Wnt signaling pathway

Liu

Tan

et al. 2019

Anti-Cancer Drugs

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“…It was well recognized that a series of genes involved in LPS-induced in ammation [18][19][20]. In this study, the DE mRNAs functional enrichment results showed that these genes were related to some biological processes, including in ammatory response, immune response, cytokine activity, chemokine activity, cytokine-cytokine receptor interaction, TNF signal pathway, NF-κB signal pathway, JAK-STAT signal pathway, NOD-like receptor signal pathway and TLR signal pathway, which were closely associated with LPS-induced in ammation [21][22][23][24][25]. In addition, though the IPA network analysis, we identi ed some genes might play key roles in LPS-induced in ammation, including NTRK1, S100A8, S100A9, TNFAIP3, TNIP1, TAX1BP1 and NOD2.…”

Section: Discussionmentioning

confidence: 57%

Construction and Analysis for Dysregulated lncRNAs and mRNAs in Lipopolysaccharide-Induced Porcine Peripheral Blood Mononuclear Cells

Zhang

Chen

et al. 2020

Preprint

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Background: Lipopolysaccharide (LPS) in the outer membrane of Gram-negative bacteria induces an intense inflammatory response in pigs. Long noncoding RNAs (lncRNAs) are emerging as key regulators in inflammation and immunity. However, their functions and profiles in LPS-induced inflammation in pigs are largely unknown. In this study, we profiled global lncRNA and mRNA expression changes in porcine peripheral blood mononuclear cells (PBMCs) treated with lipopolysaccharide (LPS) using lncRNA-seq technique. Result: Totally 43 differentially expressed (DE) lncRNAs and 1082 DE mRNAs were identified in the porcine PBMCs after LPS stimulation. Functional enrichment analysis on DE mRNAs indicated that these genes were involved in inflammation-related signaling pathways, including cytokine-cytokine receptor interaction, TNF, NF-κB, Jak-STAT and TLR signaling pathways. Additionally, co-expression network and function analysis identified the potential lncRNAs related to inflammatory response and immune response. The expression of eight lncRNAs (ENSSSCT00000045208, ENSSSCT00000051636, ENSSSCT00000049770, ENSSSCT00000050966, ENSSSCT00000047491, ENSSSCT00000049750, ENSSSCT00000054262 and ENSSSCT00000044651) was validated in the LPS- treated and non-treated PBMCs by quantitative real-time PCR (qRT-PCR). In LPS-challenged piglets, we identified that three lncRNAs (ENSSSCT00000051636, ENSSSCT00000049770, and ENSSSCT00000047491) were significantly up-regulated in liver, spleen and jejunum tissues after LPS challenge, which revealed that these lncRNAs might be important regulators for inflammation .Conclusion: This study provides the first lncRNA and mRNA transcriptomic landscape of LPS-mediated changes in porcine PBMCs. These findings may provide potential insights into lncRNAs involved in regulating immune and inflammation in pigs.

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“…nAChR knockdown in LPS-activated M s. 21,38 These results suggested that 7 nAChR might be a novel mediator of the anti-inflammatory properties of SIN. Moreover, we noted that 7 nAChR participates in FLS proliferation and the process of RA in adjuvant arthritic rat.…”

Section: Discussionmentioning

confidence: 84%

“…In clinical settings, SIN preparations are used for RA treatment with evident curative effects and no severe side effects 37 . In our previous study, we observed that the anti‐inflammatory effects of SIN can be arrested by α‐BTX and α7 nAChR knockdown in LPS‐activated Mϕs 21,38 . These results suggested that α7 nAChR might be a novel mediator of the anti‐inflammatory properties of SIN.…”

Section: Discussionmentioning

confidence: 88%

Inhibitory effect of sinomenine on lung cancer cells via negative regulation of α7 nicotinic acetylcholine receptor

Bai

Wen

Hou

et al. 2020

Journal of Leukocyte Biology

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Lung cancer is the leading cause of cancer deaths worldwide, with a high morbidity and less than 20% survival rate. Therefore, new treatment strategies and drugs are needed to reduce the mortality of patients with lung cancer. 7 nicotinic acetylcholine receptor (7 nAChR), as a receptor of nicotine and its metabolites, is a potential target for lung cancer treatment. Our previous studies revealed that sinomenine plays anti-inflammation roles via 7 nAChR and down-regulates the expression of this receptor, thus increasing the inflammatory response. Hence, sinomenine is possibly a natural ligand of this receptor. In the present study, the effects of sinomenine on lung cancer A549 cells and tumor-bearing mice were determined to investigate whether this alkaloid has an inhibitory effect on lung cancer via 7 nAChR. CCK-8 assay, wound-healing test, and flow cytometry were performed for cell proliferation, cell migration, and apoptosis analysis in vitro, respectively. Xenograft mice were used to evaluate the effects of sinomenine in vivo. Results showed that sinomenine decreased cell proliferation and migration abilities but increased the percentage of apoptotic cells. Tumor volume in tumor-bearing mice was significantly reduced after sinomenine treatment compared with that in the vehicle group mice (p < 0.05). Furthermore, the effects of sinomenine were abolished by the 7 nAChR antagonist mecamylamine and the allosteric modulator PNU-120596, but no change occurred when the mice were pretreated with the muscarinic acetylcholine receptor antagonist atropine. Meanwhile, sinomenine suppressed 7 nAChR expression in vitro and in vivo, as well as the related signaling molecules pERK1/2 and ERK1/2 and the transcription factors TTF-1 and SP-1. By contrast, sinomenine up-regulated the expression of another transcription factor, Egr-1. These effects were restricted by mecamylamine and PNU but not by atropine. Results suggested that sinomenine can inhibit lung cancer via 7 nAChR in a negative feedback mode.

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Sinomenine regulates CD14/TLR4, JAK2/STAT3 pathway and calcium signal via α7nAChR to inhibit inflammation in LPS-stimulated macrophages

Cited by 38 publications

References 24 publications

Sinomenine sensitizes human gastric cancer cells to cisplatin through negative regulation of PI3K/AKT/Wnt signaling pathway

Sinomenine sensitizes human gastric cancer cells to cisplatin through negative regulation of PI3K/AKT/Wnt signaling pathway

Construction and Analysis for Dysregulated lncRNAs and mRNAs in Lipopolysaccharide-Induced Porcine Peripheral Blood Mononuclear Cells

Inhibitory effect of sinomenine on lung cancer cells via negative regulation of α7 nicotinic acetylcholine receptor

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