Thrombospondin-1 Production Regulates the Inflammatory Cytokine Secretion in THP-1 Cells Through NF-κB Signaling Pathway

Tian, Xing; Wang, Yao; Ding, Wenjie; Li, Yuan-ling; Hu, Xiaodong; Wang, Cong; Ding, Ao; Shen, Jilong

doi:10.1007/s10753-017-0601-x

Cited by 30 publications

(21 citation statements)

References 52 publications

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“…In addition, previous studies showed that by disrupting the interaction between CD47 and CD14 on human macrophages, TSP-1 limited the activation of NF-κB/AP-1 by LPS, resulting in inhibition of inflammatory cytokine production [43]. In the present study, however, addition of neutralizing antibodies against TSP-1 to DFSC-CM had little effect on the expression levels of IL-6, TNF-α and iNOS of macrophages, which may be due to the different regulatory effects of TSP-1 in different environments [43,66,67]. Intriguingly, we found that IL-10 expression was not significantly reduced by the addition of either TGF-β3 or TSP-1 neutralizing antibodies, but IL-10 was significantly inhibited when both neutralizing antibodies were added to DFSC-CM.…”

Section: Cellular Physiology and Biochemistrycontrasting

confidence: 59%

Dental Follicle Stem Cells Ameliorate Lipopolysaccharide-Induced Inflammation by Secreting TGF-β3 and TSP-1 to Elicit Macrophage M2 Polarization

Chen

Yang

Tian

et al. 2018

Cell Physiol Biochem

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Background/Aims: Increasing evidence has demonstrated the novel roles of mesenchymal stem cells (MSCs) in immunotherapy. However, difficulty in acquiring these cells and possible ethical issues limited their application. Recently, we have isolated a unique MSC population from dental follicles with potent stem cell-like properties. This study focused on the effects of dental follicle stem cells (DFSCs) on macrophage activation and polarization to determine their role in immunomodulation and to test if DFSCs are a promising cell source for MSC-based immunotherapy. Methods: Rat acute lung injury (ALI) models induced by Lipopolysaccharide (LPS) were applied to test the immune-modulatory effects of DFSC/DFSC-CM in vivo. The pulmonary permeability was determined by the dry / wet weight ratios of the left upper lung lobe. The lung histopathological damage was graded on a 0 to 4+ scale. And the inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were tested by ELISA. Then we established LPS-induced inflamed macrophage models in vitro. Inflammatory cytokine production and polarization marker expression were measured by RT-qPCR, ELISA, western blot and flow cytometric analysis in macrophages following DFSC-CM treatment. The paracrine factors in DFSC-CM were revealed by a RayBiotech Protein Array. Thereafter, neutralization studies were performed to confirm the potential immune regulators in DFSC-CM. Results: The DFSC/DFSC-CM not only attenuated histopathological damage and pulmonary permeability, but also downregulated pro-inflammatory cytokines MCP-1, IL-1, IL-6 and TNF-α, and upregulated anti-inflammatory cytokine IL-10 in BALF. Immunofluorescence staining revealed the increased expression of macrophage M2 marker Arg-1. Further in vitro study revealed that macrophages switched to an anti-inflammatory M2 phenotype when co-cultured with DFSC-CM, characterized by suppressed production of pro-inflammatory cytokines MCP-1, IL-1, IL-6, TNF-α and M1-polarizing markers iNOS and CD86; and increased expression of the anti-inflammatory cytokine IL-10 and the M2-polarizing markers Arg-1 and CD163. A RayBiotech Protein Array revealed 42 differentially expressed (> 2-fold) paracrine factors in DFSC-CM compared with the serum-free Ham’s F-12K medium, among which TGF-β3 and Thrombospondin-1 (TSP-1) were upregulated by 18- and 105-fold, respectively. Neutralization studies confirmed the immunoregulatory roles of TGF-β3 and TSP-1 in macrophage activation and polarization. Conclusion: These results indicated that DFSCs can reprogram macrophages into the anti-inflammatory M2 phenotype, the paracrine factors TGF-β3 and TSP-1 may be one of the underlying mechanisms. This study supports the hypothesis that DFSCs are promising for MSC-based immunotherapy.

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Section: Cellular Physiology and Biochemistrycontrasting

confidence: 59%

Dental Follicle Stem Cells Ameliorate Lipopolysaccharide-Induced Inflammation by Secreting TGF-β3 and TSP-1 to Elicit Macrophage M2 Polarization

Chen

Yang

Tian

et al. 2018

Cell Physiol Biochem

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“…Although the underlying mechanism was not revealed in this study, we speculate that PERK-elf2-ATF-4-CHOP signaling pathway plays an important role since only PERK signaling pathway was activated in our model. A large number of studies have shown that interference or knockout of CHOP could significantly decrease the production of TGF-β1 [40,41], which could be associated with suppressing NF-κB signaling [39] since NF-κB is a major regulator to modulate the expression of TSP-1 and TGF-β1 [42,43].…”

Section: Discussionmentioning

confidence: 99%

Attenuation of intermittent hypoxia-induced apoptosis and fibrosis in pulmonary tissues via suppression of ER stress activation

Shi

Xie

et al. 2020

BMC Pulm Med

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Background: Obstructive sleep apnea (OSA) is associated with pulmonary fibrosis and endothelial apoptosis in pulmonary tissues. Chronic intermittent hypoxia (IH) is considered to be the primary player in OSA, but the mechanisms underlying its effect on pulmonary tissues are unknown. Endoplasmic reticulum (ER) stress induced by IH treatment plays an important role in accelerating the process of fibrosis and induction of apoptosis. Methods: Mice were placed in IH chambers for 4 weeks with an oscillating oxygen (O 2 ) concentration between 5 and 21%, cycling every 90s for 8 h daily. Mice were randomly divided into four groups: control group (normal oxygen), tauroursodeoxycholic acid (TUDCA) group (normal oxygen intraperitoneally injected with TUDCA), IH group and IH + TUDCA group. After 4 weeks, the proteins in three branch signaling pathways of ER stress, including protein kinase RNA (PKR)-like/Pancreatic ER kinase (PERK), activating transcription factor 6 (ATF-6) and inositolrequiring enzyme 1 (IRE-1), were evaluated. The cleaved caspase-3, caspase-12 and TUNNEL staining was assessed. Furthermore, the expression of transforming growth factor-β1 (TGF-β1) and thrombospondin-1(TSP-1), two extracellular matrix proteins that play critical role in fibrosis, were examined. Finally, Masson's trichrome staining was performed to detect the expression of collagen. Results: After 4 weeks of IH treatment, the expressions of two ER stress markers, glucose regulated protein-78 (Grp78) and transcription factor C/EBP homologous protein (CHOP) were increased which was prevented by administration of the ER stress attenuator, TUDCA. The expressions of PERK, but not those of ATF-6 and IRE-1, were increased. The effects of IH were accompanied by an increased number of apoptotic cells and increased expressions of cleaved caspase-3 and caspase-12 in pulmonary tissues. In addition, histological examination suggested the presence of fibrosis after chronic IH treatment, indicated by increased expression of collagen, which was associated with the up-regulation of TGF-β1 and TSP-1 that are known to promote fibrosis. Similarly, TUDCA could reduce the extent of fibrotic area and the expression levels of these proteins. (Continued on next page)Conclusions: It reveals the roles of ER stress, especially the PERK pathway, in IH induced apoptosis and fibrosis in pulmonary tissues that might underlie the pulmonary complications observed in OSA.

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“…Cells do not have a cuboid shape, rather have a flat surface were considered as surface lining cells which are not active osteoblast producing osteoid and were not counted. Regarding the inflammatory cells, fibroblast cells and endothelial cells could easily be differentiated from inflammatory cells which were macrophage, neutrophil, eosinophil, T lymphocytes, and plasma cells . Fibroblasts have a thin and long spindle‐like shape, while other cells have a more rounded shape .…”

Section: Methodsmentioning

confidence: 99%

“…Regarding the inflammatory cells, fibroblast cells and endothelial cells could easily be differentiated from inflammatory cells which were macrophage, neutrophil, eosinophil, T lymphocytes, and plasma cells. [28][29][30][31][32][33] Fibroblasts have a thin and long spindle-like shape, while other cells have a more rounded shape. 28,29,[31][32][33][34] The cells which were not easily differentiated were not counted.…”

Section: Histologic Evaluationmentioning

confidence: 99%

Evaluation of the effect of oleuropein on alveolar bone loss, inflammation, and apoptosis in experimental periodontitis

Taşkan

Yüce

Karataş

et al. 2019

J of Periodontal Research

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The Objective The present study aimed to evaluate the effects of oleuropein on ligature‐induced alveolar bone loss. In this respect, osteoblastic activity, osteoclastic activity, inflammatory markers, and apoptosis were evaluated. Background Oleuropein is a flavonoid, which has potent anti‐inflammatory and bone‐protective effects. Methods Thirty‐two Wistar rats were divided into four experimental groups as following: control (C, n = 8) group; periodontitis (P, n = 8) group; periodontitis and low‐dose oleuropein group (12 mg/kg/day oleuropein, LDO group, n = 8); and periodontitis and high‐dose oleuropein group (24 mg/kg/day oleuropein, HDO group, n = 8). Periodontitis was induced via ligatures. Study period was 14 days, and animals were sacrificed at end of this period. Mandibles were examined via a stereomicroscope and underwent histological procedures. Osteoblast, tartrate‐resistant acid phosphatase (TRAP)‐positive osteoclast, and inflammatory cell counts were determined in hematoxylin‐eosin stained sections. Inducible nitric oxide synthase (iNOS), bone morphogenetic protein‐4, the cluster of differentiation (CD)‐68, cysteine‐aspartic proteases‐3 (Caspase 3), and B‐cell lymphoma‐2 (Bcl‐2) expressions were evaluated via immunohistochemistry. Results Periodontitis group had highest alveolar bone loss, and these levels significantly decreased in LDO and HDO groups. Both 12 and 24 mg/kg oleuropein groups significantly increased osteoblast cell counts and decreased TRAP‐positive osteoclast and inflammatory cell counts. BMP‐4 and bcl‐2 expressions were elevated in oleuropein groups while caspase‐3 expressions decreased. iNOS and CD68 were higher in periodontitis group compared to control group, but there was no significant difference between other groups. Conclusion Oleuropein successfully decreased alveolar bone loss as a result of decreased osteoclastic activity, inflammation, and apoptosis and increased osteoblastic activity.

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Thrombospondin-1 Production Regulates the Inflammatory Cytokine Secretion in THP-1 Cells Through NF-κB Signaling Pathway

Cited by 30 publications

References 52 publications

Dental Follicle Stem Cells Ameliorate Lipopolysaccharide-Induced Inflammation by Secreting TGF-β3 and TSP-1 to Elicit Macrophage M2 Polarization

Dental Follicle Stem Cells Ameliorate Lipopolysaccharide-Induced Inflammation by Secreting TGF-β3 and TSP-1 to Elicit Macrophage M2 Polarization

Attenuation of intermittent hypoxia-induced apoptosis and fibrosis in pulmonary tissues via suppression of ER stress activation

Evaluation of the effect of oleuropein on alveolar bone loss, inflammation, and apoptosis in experimental periodontitis

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