Attenuation of neutrophil-mediated liver injury in mice by drug-free E-selectin binding polymer

Milošević, Nenad; Rütter, Marie; Ventura, Yvonne; Kezerle, Yarden; Feinshtein, Valeria; David, Ayelet

doi:10.1016/j.jconrel.2019.12.018

Cited by 15 publications

(15 citation statements)

References 54 publications

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“…These molecules include cytokines, lipid peroxides, growth factors, and reactive oxygen species, which regulate HSC activities and proliferation (Tsuchida and Friedman, 2017). In addition, bone marrow-derived monocytes massively accumulate in the injured liver and differentiate into inflammatory macrophages (Milosevic et al, 2019). Neutrophils are the rapid and first line of defense against many pathogenic microorganisms.…”

Section: Discussionmentioning

confidence: 99%

Disruption of FGF Signaling Ameliorates Inflammatory Response in Hepatic Stellate Cells

Zhang

et al. 2020

Front. Cell Dev. Biol.

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It is a well-documented event that fibroblast growth factors (FGFs) regulate liver development and homeostasis in autocrine, paracrine, and endocrine manners via binding and activating FGF receptors (FGFRs) tyrosine kinase in hepatocytes. Recent research reveals that hepatic stellate cells (HSCs) play a fundamental role in liver immunology. However, how FGF signaling in HSCs regulates liver inflammation remains unclear. Here, we report that FGF promoted NF-κB signaling, an inflammatory pathway, in human HSCs, which was associated with FGFR1 expression. Both FGF and NF-κB signaling in HSCs were compromised by FGFR1 tyrosine kinase inhibitor. After stimulating HSCs with proinflammatory cytokines, expression of multiple FGF ligands was significantly increased. However, disruption of FGF signaling with FGFR inhibitors prominently reduced the apoptosis, inflammatory response, NF-κB nuclear translocation, and expression of matrix metalloproteinase-9 (MMP-9) induced by TNFα in HSCs. Interestingly, FGF21 significantly alleviated the inflammation responses in the concanavalin A (Con A)-induced acutely injured liver. Unlike canonic FGFs that elicit signals through activating the FGFR-heparan sulfate complex, FGF21 activates the FGFR-KLB complex and elicits a different set of signals. Therefore, the finding here indicates the urgency of developing pathway-specific inhibitors that only suppress canonical FGF, but not non-canonical FGF21, signaling for alleviating inflammation in the liver, which is presented in all stages of diseased liver.

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Section: Discussionmentioning

confidence: 99%

Disruption of FGF Signaling Ameliorates Inflammatory Response in Hepatic Stellate Cells

Zhang

et al. 2020

Front. Cell Dev. Biol.

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“…43 Furthermore, E-selectin binding peptides inhibited the supplementation of neutrophils to inflammatory sites and reduced the levels of proinflammatory factors and chemokines in an alcoholic liver model, which might be used to control liver inflammation. 44 Although there have been many reports on the negative roles of neutrophils in alcoholic hepatitis, some clinical studies have drawn different conclusions. On the one hand, the cytokines and chemokines that promote neutrophil infiltration are related to the severity of alcoholic hepatitis by increasing ROS, proteases, and inflammatory mediators, which promote liver inflammation and fibrosis.…”

Section: The Role Of Neutrophils In Alcoholic Liver Diseasementioning

confidence: 99%

Neutrophils in liver diseases: pathogenesis and therapeutic targets

Wang

Xu³

2020

Cell Mol Immunol

122

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Previously, it was assumed that peripheral neutrophils are a homogeneous population that displays antimicrobial functions. However, recent data have revealed that neutrophils are heterogeneous and are additionally involved in tissue damage and immune regulation. The phenotypic and functional plasticity of neutrophils has been identified in patients with cancer, inflammatory disorders, infections, and other diseases. Currently, neutrophils, with their autocrine, paracrine, and immune modulation functions, have been shown to be involved in liver diseases, including viral hepatitis, nonalcoholic steatohepatitis, alcoholic liver disease, liver fibrosis, cirrhosis, liver failure, and liver cancer. Accordingly, this review summarizes the role of neutrophils in liver diseases.

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“…Recruiting neutrophils depends on E-selectin receptors. [7][8][9] E-and P-selectins are expressed on endothelial cells, which are affected by inflammation and bind to glycoprotein ligands on neutrophils. E-selectin has the key role in neutrophils' slowrolling on endothelial cells, and they are essential to the fungal infection site.…”

Section: Introductionmentioning

confidence: 99%

<p>An Overview of the Management of the Most Important Invasive Fungal Infections in Patients with Blood Malignancies</p>

Shariati¹,

Moradabadi²,

Chegini³

et al. 2020

IDR

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In patients with hematologic malignancies due to immune system disorders, especially persistent febrile neutropenia, invasive fungal infections (IFI) occur with high mortality. Aspergillosis, candidiasis, fusariosis, mucormycosis, cryptococcosis and trichosporonosis are the most important infections reported in patients with hematologic malignancies that undergo hematopoietic stem cell transplantation. These infections are caused by opportunistic fungal pathogens that do not cause severe issues in healthy individuals, but in patients with hematologic malignancies lead to disseminated infection with different clinical manifestations. Prophylaxis and creating a safe environment with proper filters and air pressure for patients to avoid contact with the pathogens in the surrounding environment can prevent IFI. Furthermore, due to the absence of specific symptoms in IFI, rapid and accurate diagnosis reduces the mortality rate of these infections and using molecular techniques along with standard mycological methods will improve the diagnosis of disseminated fungal infection in patients with hematologic disorders. Amphotericin B products, extended-spectrum azoles, and echinocandins are the essential drugs to control invasive fungal infections in patients with hematologic malignancies, and according to various conditions of patients, different results of treatment with these drugs have been reported in different studies. On the other hand, drug resistance in recent years has led to therapeutic failures and deaths in patients with blood malignancies, which indicates the need for antifungal susceptibility tests to use appropriate therapies. Life-threatening fungal infections have become more prevalent in patients with hematologic malignancies in recent years due to the emergence of new risk factors, new species, and increased drug resistance. Therefore, in this review, we discuss the different dimensions of the most critical invasive fungal infections in patients with hematologic malignancies and present a list of these infections with different clinical manifestations, treatment, and outcomes.

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Attenuation of neutrophil-mediated liver injury in mice by drug-free E-selectin binding polymer

Cited by 15 publications

References 54 publications

Disruption of FGF Signaling Ameliorates Inflammatory Response in Hepatic Stellate Cells

Disruption of FGF Signaling Ameliorates Inflammatory Response in Hepatic Stellate Cells

Neutrophils in liver diseases: pathogenesis and therapeutic targets

<p>An Overview of the Management of the Most Important Invasive Fungal Infections in Patients with Blood Malignancies</p>

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