Increased proteinase 3 and neutrophil elastase plasma concentrations are associated with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes

Mirea, Andreea-Manuela; Toonen, Erik J. M.; Munckhof, Inge van den; Munsterman, Isabelle D.; Tjwa, Eric T.; Jaeger, Martin; Oosting, Marije; Schraa, Kiki; Rutten, Joost H.W.; Graaf, Marinette van der; Riksen, Niels P.; Graaf, Jacqueline de; Netea, Mihai G.; Tack, Cees J.; Chavakis, Triantafyllos; Joosten, Leo A. B.

doi:10.1186/s10020-019-0084-3

Cited by 56 publications

(38 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These factors are involved in lipid peroxidation and hepatic stellate cell migration, facilitating cellular injury and fibrosis. The key role of neutrophils in the pathogenesis of NASH diseases was supported by demonstrating the increase of circulating levels and activity of neutrophils elastase during the curse of this pathology [39,40]. In NASH animal models, these proinflammatory cells regulate the ceramide metabolism, which is also involved in the pathogenesis of NASH [41].…”

Section: Discussionmentioning

confidence: 98%

Circulating Neutrophils of Nonalcoholic Steatohepatitis Patients Show an Activated Phenotype and Suppress T Lymphocytes Activity

Antonucci¹,

Porcu²,

Timperi

et al. 2020

Journal of Immunology Research

View full text Add to dashboard Cite

Neutrophils or PolyMorphonuclear Neutrophils (PMNs) are key effector cells of the innate immune system and thanks to their remarkable plasticity, establish a cross talk with T cells modulating their survival and effector functions. During Nonalcoholic Steatohepatitis (NASH), the advanced form of hepatic steatosis or NAFL, PMNs infiltrate liver tissue, becoming a histological feature of NASH. Our aim was to evaluate the frequency of PMNs in NAFL and NASH patients in order to understand how they modulate the activity of circulating CD4+ and CD8+ T cells. In our cohort of patients, NASH patients displayed a higher frequency of circulating PMNs that was strongly correlated to liver enzymes, grade of steatosis, inflammation and fibrosis, the hepatocellular ballooning, and NAFLD Activity Score (NAS). Furthermore, even if ex vivo, in both groups of patients, PMNs shared the same phenotype of resting cells, after 24 hours of coculture with autologous CD4+ and CD8+ T cells, PMNs of NASH patients acquired a more active phenotype, becoming able to strongly inhibit proliferation and activation of CD4+ and CD8+ T cells. The higher ability of PMNs of NASH patients in suppressing CD4+ and CD8+ T cells, over time, might contribute in reducing the immunological defense of liver tissue against damages thus taking part in the progression of the NAFL disease toward NASH.

show abstract

Section: Discussionmentioning

confidence: 98%

Circulating Neutrophils of Nonalcoholic Steatohepatitis Patients Show an Activated Phenotype and Suppress T Lymphocytes Activity

Antonucci¹,

Porcu²,

Timperi

et al. 2020

Journal of Immunology Research

View full text Add to dashboard Cite

show abstract

“…232 Increased proteinase 3 and neutrophil elastase plasma concentrations are associated with NAFLD and type 2 diabetes. 237 Recent studies have demonstrated that overexpression of CXCL1 or IL-8 can induce hepatic neutrophil infiltration and promote the progression of fatty liver to NASH in high-fat diet (HFD)-fed mice, which is mediated via the p47 Phox -dependent production of ROS by neutrophils. 155 Neutrophils can release neutrophil extracellular traps (NETs) to control infection, and in humans, elevated NET markers in serum are associated with NASH severity; similarly, reducing NET release improves liver inflammation and NASH-related HCC in mouse models.…”

Section: Microbial Dysbiosis and Intestinal Barrier Functionmentioning

confidence: 99%

“… 232 Increased proteinase 3 and neutrophil elastase plasma concentrations are associated with NAFLD and type 2 diabetes. 237 …”

Section: Immunological Mechanisms Of Nafldmentioning

confidence: 99%

Immunological mechanisms and therapeutic targets of fatty liver diseases

et al. 2020

View full text Add to dashboard Cite

Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are the two major types of chronic liver disease worldwide. Inflammatory processes play key roles in the pathogeneses of fatty liver diseases, and continuous inflammation promotes the progression of alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH). Although both ALD and NAFLD are closely related to inflammation, their respective developmental mechanisms differ to some extent. Here, we review the roles of multiple immunological mechanisms and therapeutic targets related to the inflammation associated with fatty liver diseases and the differences in the progression of ASH and NASH. Multiple cell types in the liver, including macrophages, neutrophils, other immune cell types and hepatocytes, are involved in fatty liver disease inflammation. In addition, microRNAs (miRNAs), extracellular vesicles (EVs), and complement also contribute to the inflammatory process, as does intertissue crosstalk between the liver and the intestine, adipose tissue, and the nervous system. We point out that inflammation also plays important roles in promoting liver repair and controlling bacterial infections. Understanding the complex regulatory process of disrupted homeostasis during the development of fatty liver diseases may lead to the development of improved targeted therapeutic intervention strategies.

show abstract

“…NASH is characterized by hepatic neutrophil infiltration ( 79 ). The ratio of NE to α1-antitrypsin ( 108 ), plasma concentration of PR3 and NE ( 109 ), neutrophil-to-lymphocyte ratio ( 110 ), serum levels of LCN2 ( 111 ), NETs ( 68 ), and MPO ( 112 ) significantly increase in patients with NAFLD. And elevated MMP9 from the neutrophils drives the NASH and fibrosis progress ( 63 ).…”

Section: Neutrophils and Chronic Liver Inflammationmentioning

confidence: 99%

The Roles of Neutrophils in the Pathogenesis of Liver Diseases

et al. 2021

View full text Add to dashboard Cite

Neutrophils are the largest population of circulating leukocytes and the first responder against invading pathogens or other danger signals. Sophisticated machineries help them play critical roles in immunity and inflammation, including phagocytosis, superoxide production, cytokine and chemokine production, degranulation, and formation of neutrophil extracellular traps (NETs). After maturation and release from the bone marrow, neutrophils migrate to inflamed tissues in response to many stimuli. Increasing evidences indicate that neutrophils are critically involved in the pathogenesis of liver diseases, including liver cancer, thus making them promising target for the treatment of liver diseases. Here, we would like to provide the latest finding about the role of neutrophils in liver diseases and discuss the potentiality of neutrophils as target for liver diseases.

show abstract

Increased proteinase 3 and neutrophil elastase plasma concentrations are associated with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes

Cited by 56 publications

References 24 publications

Circulating Neutrophils of Nonalcoholic Steatohepatitis Patients Show an Activated Phenotype and Suppress T Lymphocytes Activity

Circulating Neutrophils of Nonalcoholic Steatohepatitis Patients Show an Activated Phenotype and Suppress T Lymphocytes Activity

Immunological mechanisms and therapeutic targets of fatty liver diseases

The Roles of Neutrophils in the Pathogenesis of Liver Diseases

Contact Info

Product

Resources

About