scholarly journals Marein prevented LPS-induced osteoclastogenesis by regulating the NF-κB pathway in vitro

Author(s):  
Yuling Li ◽  
Jing Zhang ◽  
Caiping Yan ◽  
Qian Chen ◽  
Chao Xiang ◽  
...  

Abstract Gram-negative bacterial infection causes many bone diseases such as osteolysis, osteomyelitis and septic arthritis. Lipopolysaccharide (LPS), a bacteria product, played an important role in this process. Drugs that inhibited LPS-induced osteoclastogenesis were urgently needed for the prevention of bone destruction in infective bone diseases. Marein, a major bioactive compound of Coreopsis.tinctoria, which possesses anti-oxidative, anti-inflammatory, anti-hypertensive, anti-hyperlipidemic and anti-diabetic effects. In this study, the effect of marein on RAW264.7 cells was measured by CCK-8 assay; TRAP staining was used to determine osteoclastogenesis; the levels of osteoclast-related genes and NF-κB-related proteins were analyzed by WB; the levels of pro-inflammatory cytokines were quantified by ELISA. Our results showed that marein inhibited LPS-induced osteoclast formation from osteoclast precursor RAW264.7 cells. The effect of marein was related to its inhibitory function on expressions of pro-inflammatory cytokines and osteoclast-related genes including RANK, TRAF6, MMP-9, CK and CAⅡ. Besides, marein treatment could inhibit LPS-induced activation of NF-κB signaling pathway in RAW264.7 cells. Meanwhile, inhibition of NF-κB signaling pathway decreased the formation of osteoclasts and expression of pro-inflammatory cytokines which were LPS-induced. Collectively, marein could prevent LPS-induced osteoclast formation in vitro by regulating NF-κB signaling pathway. These findings provided evidence that marein might be beneficial as a valuable choice for the prevention and treatment of bacteria-induced bone destruction disease, and gave new insights for understanding its possible mechanism.

2020 ◽  
Author(s):  
Yuling Li ◽  
Jing Zhang ◽  
Caiping Yan ◽  
Qian Chen ◽  
Chao Xiang ◽  
...  

Abstract BackgroundLipopolysaccharide (LPS), a bacteria product, plays an important role in orthopedic diseases. Drugs that inhibit LPS-induced osteoclastogenesis are urgently needed for the prevention of bone destruction.MethodsIn this study, we evaluated the effect of β-ecdysterone (β-Ecd), a major component of Chinese herbal medicines derived from the root of Achyranthes bidentata BI on LPS-induced osteoclastogenesis in vitro and explored the mechanism underlying the effects of β-Ecd on this.ResultsWe showed that β-Ecd inhibited LPS-induced osteoclast formation from osteoclast precursor RAW264.7 cells. The inhibition occurred through suppressing the production of osteoclast activating TNF-α, IL-1β, PGE2 and COX-2, which led to down-regulating expression of osteoclast-related genes including RANK, TRAF6, MMP-9, CK and CAⅡ. Besides, β-Ecd treatment can inhibit LPS-induced activation of NF-κB signaling pathway in RAW264.7 cells. Meanwhile, inhibition of NF-κB signaling pathway decreased the formation of osteoclasts and expression of pro-inflammatory cytokines which LPS-induced. Collectively, β-Ecd can prevent LPS-induced osteoclast formation in vitro by regulating NF-κB signaling pathway.ConclusionsThese findings provide evidences that β-Ecd might be beneficial as a valuable choice for the prevention and treatment of bacteria-induced bone destruction disease, and give new insights for understanding its possible mechanism.


2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Hideki Kitaura ◽  
Keisuke Kimura ◽  
Masahiko Ishida ◽  
Haruka Kohara ◽  
Masako Yoshimatsu ◽  
...  

Tumor necrosis factor-α(TNF-α) is a cytokine produced by monocytes, macrophages, and T cells and is induced by pathogens, endotoxins, or related substances. TNF-αmay play a key role in bone metabolism and is important in inflammatory bone diseases such as rheumatoid arthritis. Cells directly involved in osteoclastogenesis include macrophages, which are osteoclast precursor cells, osteoblasts, or stromal cells. These cells express receptor activator of NF-κB ligand (RANKL) to induce osteoclastogenesis, and T cells, which secrete RANKL, promote osteoclastogenesis during inflammation. Elucidating the detailed effects of TNF-αon bone metabolism may enable the identification of therapeutic targets that can efficiently suppress bone destruction in inflammatory bone diseases. TNF-αis considered to act by directly increasing RANK expression in macrophages and by increasing RANKL in stromal cells. Inflammatory cytokines such as interleukin- (IL-) 12, IL-18, and interferon-γ(IFN-γ) strongly inhibit osteoclast formation. IL-12, IL-18, and IFN-γinduce apoptosis in bone marrow cells treated with TNF-α  in vitro, and osteoclastogenesis is inhibited by the interactions of TNF-α-induced Fas and Fas ligand induced by IL-12, IL-18, and IFN-γ. This review describes and discusses the role of cells concerned with osteoclast formation and immunological reactions in TNF-α-mediated osteoclastogenesisin vitroandin vivo.


2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Bo Ding ◽  
Chengheng Lin ◽  
Qian Liu ◽  
Yingying He ◽  
John Bosco Ruganzu ◽  
...  

Abstract Background Glial activation and neuroinflammation play a crucial role in the pathogenesis and development of Alzheimer’s disease (AD). The receptor for advanced glycation end products (RAGE)-mediated signaling pathway is related to amyloid beta (Aβ)-induced neuroinflammation. This study aimed to investigate the neuroprotective effects of tanshinone IIA (tan IIA), a natural product isolated from traditional Chinese herbal Salvia miltiorrhiza Bunge, against Aβ-induced neuroinflammation, cognitive impairment, and neurotoxicity as well as the underlying mechanisms in vivo and in vitro. Methods Open-field test, Y-maze test, and Morris water maze test were conducted to assess the cognitive function in APP/PS1 mice. Immunohistochemistry, immunofluorescence, thioflavin S (Th-S) staining, enzyme-linked immunosorbent assay (ELISA), real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and western blotting were performed to explore Aβ deposition, synaptic and neuronal loss, microglial and astrocytic activation, RAGE-dependent signaling, and the production of pro-inflammatory cytokines in APP/PS1 mice and cultured BV2 and U87 cells. Results Tan IIA treatment prevented spatial learning and memory deficits in APP/PS1 mice. Additionally, tan IIA attenuated Aβ accumulation, synapse-associated proteins (Syn and PSD-95) and neuronal loss, as well as peri-plaque microgliosis and astrocytosis in the cortex and hippocampus of APP/PS1 mice. Furthermore, tan IIA significantly suppressed RAGE/nuclear factor-κB (NF-κB) signaling pathway and the production of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in APP/PS1 mice and cultured BV2 and U87 cells. Conclusions Taken together, the present results indicated that tan IIA improves cognitive decline and neuroinflammation partly via inhibiting RAGE/NF-κB signaling pathway in vivo and in vitro. Thus, tan IIA might be a promising therapeutic drug for halting and preventing AD progression.


2018 ◽  
Vol 74 (1) ◽  
pp. 6045-2018 ◽  
Author(s):  
Iwona Puzio ◽  
Grzegorz Tymicki ◽  
Hanna Predka ◽  
Wiesław Śleboda ◽  
Magdalena Sobczyńska-Wołejszo

NUCB2/nesfatin-1, a member of the adipokine family, is a peptide hormone with pleiotropic action. It has been found in different tissues, including cartilage and bone cells. Nesfatin-1 is produced by chondrocytes, and its synthesis increases with the degree of cell differentiation and upon stimulation by pro-inflammatory cytokines, as shown in an in vitro study. An increase in serum levels of nesfatin-1 has been observed in humans with osteoarthritis, which indicates the influence of pro-inflammatory cytokines on nesfatin-1 release. On the other hand, nesfatin-1 stimulates the synthesis of pro-inflammatory cytokines by chondrocytes, which suggests its participation, together with other adipokines, in the pathogenesis and/or progression of inflammatory complications of cartilage degenerative diseases. Nesfatin-1 also promotes pre-osteoblastic cell differentiation and mineralization and inhibits macrophage differentiation towards osteoclasts. Moreover, exogenous nesfatin-1 given to ovariectomized rats reduces osteopenic changes. Therefore, it seems that nesfatin-1 may play a protective role in cartilage and bone diseases. However, further studies are required to determine whether nesfatin-1 can be used for monitoring and treatment of cartilage and bone diseases..


2020 ◽  
Vol 21 (15) ◽  
pp. 5240
Author(s):  
Wonyoung Seo ◽  
Suhyun Lee ◽  
Phuong Thao Tran ◽  
Thi Quynh-Mai Ngo ◽  
Okwha Kim ◽  
...  

Olean-12-en-27-oic acids possess a variety of pharmacological effects. However, their effects and underlying mechanisms on osteoclastogenesis remain unclear. This study aimed to investigate the anti-osteoclastogenic effects of five olean-12-en-27-oic acid derivatives including 3α,23-isopropylidenedioxyolean-12-en-27-oic acid (AR-1), 3-oxoolean-12-en-27-oic acid (AR-2), 3α-hydroxyolean-12-en-27-oic acid (AR-3), 23-hydroxy-3-oxoolean-12-en-27-oic acid (AR-4), and aceriphyllic acid A (AR-5). Among the five olean-12-en-27-oic acid derivatives, 3-hydroxyolean-12-en-27-oic acid derivatives, AR-3 and AR-5, significantly inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced mature osteoclast formation by reducing the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, F–actin ring formation, and mineral resorption activity. AR-3 and AR-5 decreased RANKL-induced expression levels of osteoclast-specific marker genes such as c-Src, TRAP, and cathepsin K (CtsK) as well as c-Fos and nuclear factor of activated T cells cytoplasmic 1 (NFATc1). Mice treated with either AR-3 or AR-5 showed significant protection of the mice from lipopolysaccharide (LPS)-induced bone destruction and osteoclast formation. In particular, AR-5 suppressed RANKL-induced phosphorylation of JNK and ERK mitogen-activated protein kinases (MAPKs). The results suggest that AR-3 and AR-5 attenuate osteoclast formation in vitro and in vivo by suppressing RANKL-mediated MAPKs and NFATc1 signaling pathways and could potentially be lead compounds for the prevention or treatment of osteolytic bone diseases.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xi Zhang ◽  
Aie Chang ◽  
Yanqiang Zou ◽  
Heng Xu ◽  
Jikai Cui ◽  
...  

Background: Dendritic cells (DCs) serve as an important part of the immune system and play a dual role in immune response. Mature DCs can initiate immune response, while immature or semi-mature DCs induce immune hyporesponsiveness or tolerance. Previous studies have shown that aspirin can effectively inhibit the maturation of DCs. However, the protective effect of aspirin on acute cardiac allograft rejection has not been studied. The aim of this study was to elucidate the effect of aspirin exert on allograft rejection.Methods: The model of MHC-mismatched (BALB/c to B6 mice) heterotopic heart transplantation was established and administered intraperitoneal injection with aspirin. The severity of allograft rejection, transcriptional levels of cytokines, and characteristics of immune cells were assessed. Bone marrow-derived dendritic cells (BMDCs) were generated with or without aspirin. The function of DCs was determined via mixed lymphocyte reaction (MLR). The signaling pathway of DCs was detected by Western blotting.Results: Aspirin significantly prolonged the survival of cardiac allograft in mouse, inhibited the production of pro-inflammatory cytokines and the differentiation of effector T cells (Th1 and Th17), as well as promoted the regulatory T cells (Treg). The maturation of DCs in the spleen was obviously suppressed with aspirin treatment. In vitro, aspirin decreased the activation of NF-κB signaling of DCs, as well as impeded MHCII and co-stimulatory molecules (CD80, CD86, and CD40) expression on DCs. Moreover, both the pro-inflammatory cytokines and function of DCs were suppressed by aspirin.Conclusion: Aspirin inhibits the maturation of DCs through the NF-κB signaling pathway and attenuates acute cardiac allograft rejection.


2021 ◽  
Vol 22 (2) ◽  
pp. 762
Author(s):  
Gi Ho Lee ◽  
Ji Yeon Kim ◽  
Sun Woo Jin ◽  
Thi Hoa Pham ◽  
Jin Song Park ◽  
...  

Inflammatory diseases are caused by excessive inflammation from pro-inflammatory mediators and cytokines produced by macrophages. The Nrf2 signaling pathway protects against inflammatory diseases by inhibiting excessive inflammation via the regulation of antioxidant enzymes, including HO-1 and NQO1. We investigated the anti-inflammatory effect of impressic acid (IPA) isolated from Acanthopanax koreanum on the lipopolysaccharide (LPS)-induced inflammation and the underlying molecular mechanisms in RAW264.7 cells. IPA attenuated the LPS-induced production of pro-inflammatory cytokines and reactive oxygen species, and the activation of the NF-κB signaling pathway. IPA also increased the protein levels of Nrf2, HO-1, and NQO1 by phosphorylating CaMKKβ, AMPK, and GSK3β. Furthermore, ML385, an Nrf2 inhibitor, reversed the inhibitory effect of IPA on LPS-induced production of pro-inflammatory cytokines in RAW264.7 cells. Therefore, IPA exerts an anti-inflammatory effect via the AMPK/GSK3β/Nrf2 signaling pathway in macrophages. Taken together, the findings suggest that IPA has preventive potential for inflammation-related diseases.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jia Sun ◽  
Xuan Sun ◽  
Junhui Chen ◽  
Xin Liao ◽  
Yixuan He ◽  
...  

Abstract Background Exosomal microRNAs (miRs) derived from mesenchymal stem cells (MSCs) have been shown to play roles in the pathophysiological processes of sepsis. Moreover, miR-27b is highly enriched in MSC-derived exosomes. Herein, we aimed to investigate the potential role and downstream molecular mechanism of exosomal miR-27b in sepsis. Methods Inflammation was induced in bone marrow-derived macrophages (BMDMs) by lipopolysaccharide (LPS), and mice were made septic by cecal ligation and puncture (CLP). The expression pattern of miR-27b in MSC-derived exosomes was characterized using RT-qPCR, and its downstream gene was predicted by in silico analysis. The binding affinity between miR-27b, Jumonji D3 (JMJD3), or nuclear factor κB (NF-κB) was characterized to identify the underlying mechanism. We induced miR-27b overexpression or downregulation, along with silencing of JMJD3 or NF-κB to examine their effects on sepsis. The production of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 was detected by ELISA. Results miR-27b was highly expressed in MSC-derived exosomes. Mechanistic investigations showed that miR-27b targeted JMJD3. miR-27b decreased expression of pro-inflammatory genes by inhibiting the recruitment of JMJD3 and NF-κB at gene promoter region. Through this, MSC-derived exosomal miR-27b diminished production of pro-inflammatory cytokines in LPS-treated BMDMs and septic mice, which could be rescued by upregulation of JMJD3 and NF-κB. Besides, in vitro findings were reproduced by in vivo findings. Conclusion These data demonstrated that exosomal miR-27b derived from MSCs inhibited the development of sepsis by downregulating JMJD3 and inactivating the NF-κB signaling pathway.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yujia Li ◽  
Bin Li ◽  
Pan Wang ◽  
Qinghua Wang

Background and Aims: Qingfei Paidu decoction (QPD) and Xuanfei Baidu decoction (XBD) are two typical traditional Chinese medicines with proven efficacy for the treatment of SARS-CoV-2, although the underlying mechanism is not well defined. Blunted immune response and enhanced production of pro-inflammatory cytokines (cytokine storm) are two main features observed in patients infected with SARS-CoV-2. Analysis based on network pharmacology has revealed that both QPD and XBD played an important role in the regulation of host immunity. We therefore investigated the role of QPD and XBD in the modulation of innate immunity in vitro, focusing on the type 1 interferon (IFN) signaling pathway in A549 cells and pro-inflammatory cytokine production in macrophages. Methods: A549 cells were treated with QPD or XBD and the production of endogenous IFNα and IFNβ as well as the expression levels of some interferon-stimulated genes (ISGs) were detected by reverse transcriptase-quantitative PCR (RT-qPCR). Macrophages derived from THP-1 cells were treated with QPD or XBD and their pro-inflammatory cytokine expression levels were measured by RT-qPCR, 6 h post LPS stimulation. In addition, the expression levels of some pro-inflammatory cytokines were further analyzed by ELISA. The effect of QPD and XBD on the NF-κB signaling pathway and the pinocytosis activity of THP-1-derived macrophages were evaluated by Western blot and neutral red uptake assay, respectively. Results: Although QPD and XBD showed very little effect on the type 1 IFN signaling pathway in A549 cells, either QPD or XBD markedly inhibited the production of pro-inflammatory markers including interleukin-6, tumor necrosis factor-α, monocyte chemotactic protein-1, and chemokine ligand 10 in THP-1-derived M1 macrophages. In addition, the phosphorylation of IκBα and NF-κB p65 during the process of macrophage polarization was significantly suppressed following QPD or XBD treatment. QPD and XBD also suppressed the pinocytosis activity of macrophages. Conclusion: QPD and XBD have been shown to have robust anti-inflammatory activities in vitro. Our study demonstrated that both QPD and XBD decreased pro-inflammatory cytokine expression, inhibited the activation of the NF-κB signaling pathway, and blunted pinocytosis activity in THP-1-derived macrophages.


Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2794 ◽  
Author(s):  
Cao ◽  
Chen ◽  
Ren ◽  
Zhang ◽  
Tan ◽  
...  

Punicalagin, a hydrolysable tannin of pomegranate juice, exhibits multiple biological effects, including inhibiting production of pro-inflammatory cytokines in macrophages. Autophagy, an intracellular self-digestion process, has been recently shown to regulate inflammatory responses. In this study, we investigated the anti-inflammatory potential of punicalagin in lipopolysaccharide (LPS) induced RAW264.7 macrophages and uncovered the underlying mechanisms. Punicalagin significantly attenuated, in a concentration-dependent manner, LPS-induced release of NO and decreased pro-inflammatory cytokines TNF-α and IL-6 release at the highest concentration. We found that punicalagin inhibited NF-κB and MAPK activation in LPS-induced RAW264.7 macrophages. Western blot analysis revealed that punicalagin pre-treatment enhanced LC3II, p62 expression, and decreased Beclin1 expression in LPS-induced macrophages. MDC assays were used to determine the autophagic process and the results worked in concert with Western blot analysis. In addition, our observations indicated that LPS-induced releases of NO, TNF-α, and IL-6 were attenuated by treatment with autophagy inhibitor chloroquine, suggesting that autophagy inhibition participated in anti-inflammatory effect. We also found that punicalagin downregulated FoxO3a expression, resulting in autophagy inhibition. Overall these results suggested that punicalagin played an important role in the attenuation of LPS-induced inflammatory responses in RAW264.7 macrophages and that the mechanisms involved downregulation of the FoxO3a/autophagy signaling pathway.


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