Inhibition of ER stress-activated JNK pathway attenuates TNF-α-induced inflammatory response in bone marrow mesenchymal stem cells

Background. Systemic inflammatory response syndrome (SIRS) accompanied by trauma can lead to multiple organ dysfunction syndrome (MODS) and even death. Early inhibition of the inflammation is necessary for damage control. Bone marrow mesenchymal stem cells (BMSCs), as a novel therapy modality, have been shown to reduce inflammatory responses in human and animal models.Methods. In this study, we used Western blot, quantitative PCR, and enzyme-linked immunosorbent assay (ELISA) to assess the activity of BMSCs to suppress the inflammation induced by lipopolysaccharide (LPS) in human umbilical cord endothelial cells (HUVECs) and alveolar macrophages.Results. Our results demonstrated that LPS caused an inflammatory response in alveolar macrophages and HUVECs, increased permeability of HUVEC, upregulated expression of toll-like receptor (TLR) 2, TLR4, phosphorylated p65, downregulated release of IL10, and promoted release of TNF-αin both cells. Coculture with BMSCs attenuated all of these activities induced by LPS in the two tested cell types.Conclusions. Together, our results demonstrate that BMSCs dosage dependently attenuates the inflammation damage of alveolar macrophages and HUVECs induced by LPS.

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N‑acetyl cysteine inhibits the lipopolysaccharide‑induced inflammatory response in bone marrow mesenchymal stem cells by suppressing the TXNIP/NLRP3/IL‑1β signaling pathway

Molecular Medicine Reports ◽

10.3892/mmr.2020.11433 ◽

2020 ◽

Author(s):

Xuemei Wang ◽

Mengyi Jiang ◽

Xiaoping He ◽

Bo Zhang ◽

Wei Peng ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Inflammatory Response ◽

Signaling Pathway ◽

Marrow Mesenchymal Stem Cells ◽

Acetyl Cysteine

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Bone marrow mesenchymal stem cells accelerate the hyperglycemic refractory wound healing by inhibiting an excessive inflammatory response

Molecular Medicine Reports ◽

10.3892/mmr.2017.6400 ◽

2017 ◽

Vol 15 (5) ◽

pp. 3239-3244 ◽

Cited By ~ 1

Author(s):

Wenbin Nan ◽

Zhihao Xu ◽

Zhibin Chen ◽

Xin Yuan ◽

Juntang Lin ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Inflammatory Response ◽

Marrow Mesenchymal Stem Cells ◽

Excessive Inflammatory Response

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MiR-128-3p mediates TNF-α-induced inflammatory responses by regulating Sirt1 expression in bone marrow mesenchymal stem cells

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2019.10.083 ◽

2020 ◽

Vol 521 (1) ◽

pp. 98-105 ◽

Cited By ~ 8

Author(s):

Liuzhong Wu ◽

Guirong Zhang ◽

Chuanbo Guo ◽

Xiangyu Zhao ◽

Danyang Shen ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Inflammatory Responses ◽

Sirt1 Expression ◽

Tnf Α ◽

Marrow Mesenchymal Stem Cells

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Effects of Melatonin on Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells in Inflammatory Environment by Regulating Mammalian Target of Rapamycin/Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2579 ◽

2021 ◽

Vol 11 (4) ◽

pp. 749-755

Author(s):

Chi Zhang ◽

Yuanhe Wang ◽

Kang Sun ◽

Dingzhu Yu ◽

Shaoqi Tian

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

Caspase 3 ◽

Akt Signaling ◽

Sod Activity ◽

Alp Activity ◽

Tnf Α ◽

Marrow Mesenchymal Stem Cells

Human bone marrow mesenchymal stem cells (BMSCs) differentiation into special cell types is affected by inflammation. Melatonin has various effects such as anti-oxidation and immune regulation. However, melatonin’s effect on BMSCs osteogenic differentiation during inflammation has not been elucidated. Rat BMSCs were isolated and assigned into control group, inflammation group (1 μg/ml lipopolysaccharide, LPS) and melatonin group (100 μM melatonin was added to LPSstimulated BMSCs cells) followed by analysis of BMSCs proliferation by MTT assay, Caspase 3 and ALP activity, expression of Runx2 and OP by Real time PCR, ROS content and SOD activity, TNF-α and IL-1β secretion by ELISA and mTOR/PI3K/AKT signaling protein level by Western blot. LPS action on BMSCs significantly inhibits BMSCs proliferation, promotes Caspase 3 activity, inhibits ALP activity, decreases Runx2 and OP expression and SOD activity, increases ROS content and TNF-α and IL-1β secretion as well as reduced mTOR and p-PI3K level (P <0.05). Melatonin addition significantly reversed the above changes (P <0.05). Melatonin can regulate oxidative stress, inhibit inflammation, and promote BMSCs proliferation and osteogenic differentiation in inflammatory environment by activating mTOR/PI3K/AKT signaling pathway.

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