Bone Marrow Mesenchymal Stem Cells Suppress Acute Lung Injury Induced by Lipopolysaccharide Through Inhibiting the TLR2, 4/NF-κB Pathway in Rats with Multiple Trauma

Li, Dequan; Pan, Xuebo; Zhao, Jingbo; Chi, Chuang; Wu, Guangyu; Wang, Yuan‐Yuan; Liao, Shunbao; Ma, Jinlong; Pan, Jingye

doi:10.1097/shk.0000000000000548

Cited by 21 publications

(13 citation statements)

References 29 publications

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“…It is reported that numerous Chinese traditional medicines can protect against LPS-induced ALI via inhibiting TLR4/NF-κB signaling, which includes Lianqinjiedu (LQJD),36 Mogroside IIIE,37 Artesunate,38 and so on. Activation of NF-κB promotes the production of inflammatory cytokines mainly through the resynthesis of IκB,39,40 leading to diffuse alveolar damage in the lung 41. Similar to these reports, our data illustrated SU5416 could inhibit LPS-evoked injury to alveolar epithelial cells and area of inflammation infiltration in lung tissues.…”

Section: Discussionsupporting

confidence: 87%

<p>SU5416 attenuated lipopolysaccharide-induced acute lung injury in mice by modulating properties of vascular endothelial cells</p>

Huang

Zhu

Jiang

et al. 2019

DDDT

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Background and aim: A potent and selective vascular endothelial growth factor receptor (VEGFR) inhibitor SU5416, has been developed for the treatment of solid human tumors. The binding of VEGF to VEGFR plays a crucial role in the pathophysiology of respiratory disorders. However, the impact of SU5416 on lipopolysaccharide (LPS)-induced acute lung injury (ALI) remains unclear. Thus, this study aimed to illuminate the biofunction of SU5416 in the mouse model of ALI. Methods: Wild-type (WT) and toll-like receptor 4 (TLR4)-deﬁcient (TLR4 −/- ) C57BL/6 mice were used to establish LPS-induced ALI model. The primary pulmonary microvascular endothelial cell (PMVEC) was extracted for detection of endothelial barrier function. Results: LPS significantly increased the number of inflammatory cells and inflammatory cytokines in bronchoalveolar lavage fluid (BALF). In addition, LPS increased alveolar epithelial cells injury, inflammation infiltration and vascular permeability of PMVEC in WT and TLR4 −/- mice. Western blotting experiment indicated VEGF/VEGFR and TLR4/NF-κB pathways were involved in the progression of LPS-stimulated ALI. Consistent with previous research, dexamethasone treatment appeared to be an effective therapeutic for mice with ALI. Moreover, treatment with SU5416 dramatically attenuated LPS-induced immune responses in mice lung tissues via inhibiting VEGF/VEGFR and TLR4/NF-κB pathways. Finally, SU5416 also decreased vascular permeability of PMVEC in vitro. Conclusion: SU5416 ameliorated alveolar epithelial cells injury and histopathological changes in mice lung via inhibiting VEGF/VEGFR and TLR4/NF-κB signaling pathways. We also confirmed that SU5416 could restrain vascular permeability in PMVEC through improving the integrity of endothelial cell. These findings suggested that SU5416 may serve as a potential agent for the treatment of patients with ALI.

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Section: Discussionsupporting

confidence: 87%

<p>SU5416 attenuated lipopolysaccharide-induced acute lung injury in mice by modulating properties of vascular endothelial cells</p>

Huang

Zhu

Jiang

et al. 2019

DDDT

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“…Excessive inflammation and pneumocyte apoptosis are the primary pathologies of ALI (26,27). MSCs are potent tools for improving these lesions (28).…”

Section: Discussionmentioning

confidence: 99%

“…MSCs are potent tools for improving these lesions (28). MSCs may exert preventive or inhibitory effects on the inflammatory response via TLR3-regualted mitogen-activated protein kinase and TLR2/4-NF-κB signaling pathway in LPS-induced lung injury (26,29). MSCs have been suggested to possess additional functions for the treatment of ALI/ARDS, including homing to inflammatory sites, differentiating into pneumocytes, secreting multiple soluble factors that may repair injured pneumocytes and performing immunomodulatory effects (8,30,31).…”

Section: Discussionmentioning

confidence: 99%

Coculture with bone marrow‑derived mesenchymal stem cells attenuates inflammation and apoptosis in lipopolysaccharide‑stimulated alveolar epithelial cells via enhanced secretion of keratinocyte growth factor and angiopoietin‑1 modulating the Toll‑like receptor‑4 signal pathway

et al. 2019

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Acute lung injury (ALI) is a common, costly and potentially lethal disease with characteristics of alveolar-capillary membrane disruption, pulmonary edema and impaired gas exchange due to increased apoptosis and pulmonary inflammation. There is no effective and specific therapy for ALI; however, mesenchymal stem cells (MSCs) have been demonstrated to be a potential option. Lipopolysaccharide (LPS) is a highly proinflammatory molecule that is used to mimic an in vivo inflammatory and damaged state in vitro. The present study investigated the effect of bone marrow-derived MSCs on an LPS-induced alveolar epithelial cell (A549 cell line) injury and its underlying mechanisms by a Transwell system. It was identified that a high LPS concentration caused a decrease in cell viability, increases in apoptosis, inflammatory cytokine release and NF-κB activity, disruption of the caspase-3/Bcl-2 ratio, upregulation of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and toll-interleukin-1 receptor domain-containing adaptor inducing interferon (TRIF) expression, and facilitation of TLR4/MyD88 and TLR4/TRIF complex formation in A549 cells. Coculture with MSCs attenuated all of these activities induced by LPS in A549 cells. In addition, an increased level of keratinocyte growth factor (KGF) and angiopoietin-1 (ANGPT1) secretion from MSCs was observed under inflammatory stimulation. KGF and/or ANGPT1 neutralizing antibodies diminished the beneficial effect of MSC conditioned medium. These data suggest that MSCs alleviate inflammatory damage and cellular apoptosis induced by LPS in A549 cells by modulating TLR4 signals. These changes may be partly associated with an increased secretion of KGF and ANGPT1 from MSCs under inflammatory conditions. These data provide the basis for development of MSC-based therapies for ALI.

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“…This idea is supported by different studies conducted in pathological conditions demonstrating that MSCs, exposed to damage associated molecular pattern (DAMP) or pathogen-associated molecular pattern (PAMP), could react by reverting the production of pro-inflammatory to anti-inflammatory molecules [23, 24] and by inducing the switch from pro-inflammatory M1 macrophages maturation to the anti-inflammatory M2 phenotype [25]. These observations open the field to the hypothesis that an enhancement of MSCs potential would benefit the progress of many orthopedic conditions.…”

Section: Mesenchymal Stem Cells: a Multimodal Tool To Treat Musculoskmentioning

confidence: 94%

Mesenchymal stem cells as therapeutic target of biophysical stimulation for the treatment of musculoskeletal disorders

et al. 2016

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BackgroundMusculoskeletal disorders are regarded as a major cause of worldwide morbidity and disability, and they result in huge costs for national health care systems. Traditional therapies frequently turned out to be poorly effective in treating bone, cartilage, and tendon disorders or joint degeneration. As a consequence, the development of novel biological therapies that can treat more effectively these conditions should be the highest priority in regenerative medicine.Main body of the abstractMesenchymal stem cells (MSCs) represent one of the most promising tools in musculoskeletal tissue regenerative medicine, thanks to their proliferation and differentiation potential and their immunomodulatory and trophic ability. Indeed, MSC-based approaches have been proposed for the treatment of almost all orthopedic conditions, starting from different cell sources, alone or in combination with scaffolds and growth factors, and in one-step or two-step procedures. While all these approaches would require cell harvesting and transplantation, the possibility to stimulate the endogenous MSCs to enhance their tissue homeostasis activity represents a less-invasive and cost-effective therapeutic strategy. Nowadays, the role of tissue-specific resident stem cells as possible therapeutic target in degenerative pathologies is underinvestigated. Biophysical stimulations, and in particular extracorporeal shock waves treatment and pulsed electromagnetic fields, are able to induce proliferation and support differentiation of MSCs from different origins and affect their paracrine production of growth factors and cytokines.Short conclusionsThe present review reports the attempts to exploit the resident stem cell potential in musculoskeletal pathologies, highlighting the role of MSCs as therapeutic target of currently applied biophysical treatments.

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Bone Marrow Mesenchymal Stem Cells Suppress Acute Lung Injury Induced by Lipopolysaccharide Through Inhibiting the TLR2, 4/NF-κB Pathway in Rats with Multiple Trauma

Abstract: Our results suggest that BMSCs suppress the inflammatory reactions through inhibition of the TLR2, 4 mediated NF-κB signal pathway, which hints that BMSCs can potentially be used to treat ALI in multiple trauma.

Cited by 21 publications

References 29 publications

<p>SU5416 attenuated lipopolysaccharide-induced acute lung injury in mice by modulating properties of vascular endothelial cells</p>

<p>SU5416 attenuated lipopolysaccharide-induced acute lung injury in mice by modulating properties of vascular endothelial cells</p>

Coculture with bone marrow‑derived mesenchymal stem cells attenuates inflammation and apoptosis in lipopolysaccharide‑stimulated alveolar epithelial cells via enhanced secretion of keratinocyte growth factor and angiopoietin‑1 modulating the Toll‑like receptor‑4 signal pathway

Mesenchymal stem cells as therapeutic target of biophysical stimulation for the treatment of musculoskeletal disorders

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