Unfractionated heparin attenuates LPS-induced IL-8 secretion via PI3K/Akt/NF-κB signaling pathway in human endothelial cells

Xu, Li‐Yan; Liu, Yina; Wang, Liang; Li, Zhiliang; Ma, Xiaochun

doi:10.1016/j.imbio.2014.10.008

Cited by 33 publications

(22 citation statements)

References 31 publications

(31 reference statements)

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“…It has been reported that VEGF and IL-8 can promote endothelial cell migration in an autocrine manner [15, 16]. In our system, cell migration rate of HUVECs was accelerated after CM treatment compared with that of the control.…”

Section: Discussionmentioning

confidence: 55%

“…VEGF and IL-8 secreted by cancer cells act as chemoattractants in promoting motility of endothelial cell during tumor angiogenesis [12-14]. It is noteworthy that VEGF and IL-8 are secreted not only by tumor cells, but also by endothelial cells, thereby enhancing endothelial cell migration and angiogenesis [15, 16] . However, the molecular mechanisms underlying the effect of autocrine VEGF and IL-8 on endothelial cell migration are not completely understood to date.…”

Section: Introductionmentioning

confidence: 99%

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Autocrine VEGF and IL-8 Promote Migration via Src/Vav2/Rac1/PAK1 Signaling in Human Umbilical Vein Endothelial Cells

Li¹,

Zhou²,

Jiang³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Pro-angiogenic factors VEGF and IL-8 play a major role in modulating the migratory potential of endothelial cells. The goal of this study was to investigate the effect of autocrine VEGF and IL-8 in the form of self-conditioned medium (CM) on human umbilical vein endothelial cells (HUVECs). Methods: Enzyme-linked immunosorbent assay (ELISA) examined the automatic secretion of VEGF and IL-8 protein by HUVECs. Western blot, small interfering RNA (siRNA), pulldown and Transwell assays were used to explore the role and the mechanism of autocrine VEGF and IL-8 in migration of HUVECs. Results: Neutralizing VEGF and IL-8 in CM significantly abrogated CM-induced migration of HUVECs. Autocrine VEGF and IL-8 increased Src phosphorylation, Rac1 activity and PAK1 phosphorylation in a time dependent manner. Additionally, blocking Rac1 activity with Rac1 siRNA largely abolished autocrine VEGF and IL-8-induced cell migration. Vav2 siRNA suppressed autocrine VEGF and IL-8-induced Rac1 activation and cell migration. Furthermore, blocking Src signaling with PP2, a specific inhibitor for Src, markedly prevented autocrine VEGF and IL-8-induced Vav2 and Rac1 activation as well as consequently cell migration. PAK1 siRNA also significantly abolished autocrine VEGF and IL-8-induced cell migration. Conclusions: We demonstrated for the first time that autocrine VEGF and IL-8 promoted endothelial cell migration via the Src/Vav2/Rac1/PAK1 signaling pathway. This finding reveals the molecular mechanism in the increase of endothelial cell migration induced by autocrine growth factors and cytokines, which is expected to provide a novel therapeutic target in vascular diseases.

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Section: Discussionmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Autocrine VEGF and IL-8 Promote Migration via Src/Vav2/Rac1/PAK1 Signaling in Human Umbilical Vein Endothelial Cells

Li¹,

Zhou²,

Jiang³

et al. 2017

Cell Physiol Biochem

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“…LNT is a β-D-glucan extracted from shiitake mushrooms (Lentinus edodes). A role for LNT in regulating the immune system has been implicated both in vivo and in vitro by several studies (13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Moreover, LNT has antitumour (23), antioxidation (24) and DNA damage repair activities (12).…”

Section: Discussionmentioning

confidence: 99%

“…The secretion of these factors by the BM is inducible. As a common inducer, the strong inflammatory agent lipopolysaccharides (LPSs) activate BM macrophages through multiple signalling pathways, such as MAPK, NF-κB (13) and PI3K-AKT (14), thereby inducing the production of various inflammatory cytokines (13) and colony-stimulating factors (15). CSF receptors (CSFRs) are located on the surface of granulocyte-committed haematopoietic progenitor, neutrophils and endothelial cells (16).…”

Section: Introductionmentioning

confidence: 99%

Lentinan mitigates therarubicin-induced myelosuppression by activating bone marrow-derived macrophages in an MAPK/NF-κB-dependent manner

Liu

et al. 2016

Oncology Reports

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Abstract. Bone marrow (BM) suppression (also known as myelosuppression) is the most common and most severe side-effect of therarubicin (THP) and thereby limits the clinical application of this anticancer agent. Lentinan (LNT), a glucan extracted from dried shiitake mushrooms (Lentinula edodes), exhibits a variety of pharmacological activities. The objectives of the present study were to determine the effect of LNT on the myelosuppression of THP-treated mice and to examine the pharmacological mechanism of these effects. In vivo experiments indicated that non-cytotoxic levels of LNT strongly increased blood myeloperoxidase (MPO) activity; improved BM structural injuries; increased the numbers of leukocytes and neutrophils in the blood and BM; elevated the blood levels of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF); and reduced the self-healing period in THP-treated mice. In vitro experiments indicated that LNT increased the viability of BM-derived macrophages (BMDMs) in a time-and dosedependent manner without toxic side-effects and markedly increased the release of G-CSF, GM-CSF and M-CSF by BMDMs. Further analyses revealed that LNT activated the NF-κB and MAPK signalling pathways and promoted the nuclear import of p65 and that BAY 11-7082 (a specific inhibitor of NF-κB) suppressed the release of G-CSF, GM-CSF and M-CSF. Furthermore, we found that U0126, SB203580 and SP600125 (specific inhibitors of ERK, p38 and JNK, respectively) markedly inhibited the IKK/IκB/

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“…This injury may be additionally influenced by HS fragments released during ESL degradation. Soluble heparin has been shown to be antiinflammatory by inhibiting LPS-induced NF-kB signaling and IL-8 secretion from pulmonary endothelium, and by binding and sequestering circulating damage-associated molecular patterns, such as extracellular nuclear proteins, high-mobility group box 1 protein, and histones (40)(41)(42)(43). Paradoxically, HS fragments released by enzymatic heparanase degradation may themselves propagate injury as a damageassociated molecular pattern (44).…”

Section: Acute Lung Injurymentioning

confidence: 99%

Heparan Sulfate in the Developing, Healthy, and Injured Lung

Haeger

Yang

Schmidt

2016

Am J Respir Cell Mol Biol

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Remarkable progress has been achieved in understanding the regulation of gene expression and protein translation, and how aberrancies in these template-driven processes contribute to disease pathogenesis. However, much of cellular physiology is controlled by non-DNA, nonprotein mediators, such as glycans. The focus of this Translational Review is to highlight the importance of a specific glycan polymer-the glycosaminoglycan heparan sulfate (HS)-on lung health and disease. We demonstrate how HS contributes to lung physiology and pathophysiology via its actions as both a structural constituent of the lung parenchyma as well as a regulator of cellular signaling. By highlighting current uncertainties in HS biology, we identify opportunities for future high-impact pulmonary and critical care translational investigations.

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Unfractionated heparin attenuates LPS-induced IL-8 secretion via PI3K/Akt/NF-κB signaling pathway in human endothelial cells

Cited by 33 publications

References 31 publications

Autocrine VEGF and IL-8 Promote Migration via Src/Vav2/Rac1/PAK1 Signaling in Human Umbilical Vein Endothelial Cells

Autocrine VEGF and IL-8 Promote Migration via Src/Vav2/Rac1/PAK1 Signaling in Human Umbilical Vein Endothelial Cells

Lentinan mitigates therarubicin-induced myelosuppression by activating bone marrow-derived macrophages in an MAPK/NF-κB-dependent manner

Heparan Sulfate in the Developing, Healthy, and Injured Lung

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