Central European Journal of Immunology最新文献

Introduction: Pyroptosis can aggravate lung injury in sepsis. It has been reported that lncRNA SNHG16 can regulate the inflammatory response. However, the role and underlying mechanism of SNHG16 in sepsis-induced pyroptosis and lung injury remain unclear.

Material and methods: To mimic septic lung injury in vitro, cells were treated with 1 µg/ml LPS. The Cell Counting Kit-8 (CCK-8) assay was performed to test cell viability. The lactate dehydrogenase (LDH) level was detected using a commercial kit. Interleukin (IL)-18 and IL-1 β secretion was tested using ELISA. Pyroptosis was investigated via flow cytometry. The relationship among SNHG16, miR-339-5p, and NLR family pyrin domain containing 1 (NLRP1) was explored using the dual luciferase assay.

Results: LPS significantly upregulated the levels of SNHG16 and NLRP1 in BEAS-2B cells. In addition, LPS significantly induced pyroptosis in BEAS2B cells, while this phenomenon was reversed by SNHG16 silencing. SNHG16 could bind with miR-339-5p, and NLRP1 was found to be the downstream mRNA of miR-339-5p. SNHG16 silencing significantly abolished the LPS-induced upregulation of NLRP1 through miR-339-5p downregulation. The upregulation of miR-339-5p inhibited the pro-apoptotic effect of LPS on BEAS-2B cells, which was abolished by NLRP1 overexpression. Furthermore, the anti-pyroptotic effect of SNHG16 siRNA was abolished by NLRP1 upregulation.

Conclusions: SNHG16 silencing reversed LPS-induced pyroptosis in BEAS-2B cells via miR-339-5p/NLRP1 axis mediation. Our study might shed new light on exploring therapeutic strategies for the treatment of septic lung injury.

The flow cytometry method could support physicians' decisions in the diagnosis and treatment monitoring of immunodeficient patients. Most clinical recommendations are focused on the search for alterations in T- and B-lymphocyte subsets, less commonly natural killer (NK) cells and granulocytes. While reference values for clinically meaningful lymphocyte subsets have been published ubiquitously among numerous countries, we have not found significant data for a population of adult Polish habitats; thus we determined reference values for T, B, and NK subsets according to sex and age. The female group showed a higher percentage of lymphocytes (CD45⁺⁺), T helper lymphocytes with a higher absolute count, as well as CD4/CD8 ratio, marginal zone-like B cells, class-switched B cells, and CD21^low B cells than the male group. The male group was found to have elevated percentages of naïve B lymphocytes, transitional B cells, and plasmablasts. A weak positive correlation with age was found among double positive T lymphocytes, natural killer T cells (NKT) lymphocytes, and CD21^low B cells. A negative correlation with age for double negative T lymphocytes, marginal zone-like B cells, and plasmablasts was noted. The results indicated the importance of creating distinct reference ranges regarding sex and age concerning immunophenotype.

Introduction: Hyperforin (HYP) has been reported to alleviate the inflammatory response. The purpose of this study was to examine the pharmacological effects of HYP on lipopolysaccharide (LPS)-induced inflammation and acute kidney injury (AKI).

Material and methods: In vitro and in vivo septic models were created using LPS-stimulated mice podocytes and LPS-injected mice. HYP (20 mg/kg/day) or antagomiR-21 (20 nM/0.1 ml; twice/week) was administered to mitigate LPS-induced AKI and podocyte apoptosis.

Results: HYP demonstrated potential as an NF-κB inhibitor, leading to enhanced survival rates in septic mice. Moreover, HYP directly hindered LPS-induced podocyte apoptosis and AKI. The underlying mechanism involves the modulation of LPS-induced transactivation of miR-21 by NF-κB. It was observed that excessive activation of the NF-κB/miR-21 signaling axis contributed to LPS-induced podocyte apoptosis and AKI. Additionally, the absence of miR-21 expression resulted in decreased LPS-induced podocyte apoptosis and amelioration of LPS-induced renal tubular injury.

Conclusions: The renoprotective effects of HYP were observed in septic mice through the inhibition of NF-κB/p65-mediated transactivation of miR-21. These findings suggest that targeting the NF-κB-miR-21 axis could be a potential therapeutic strategy for HYP in the prevention of AKI.

Eosinophilia is a feature of multiple conditions, both hematologic and non-hematologic, and may be associated with organ damage. The pathogenesis of eosinophilia can follow two distinct pathways. Primary eosinophilia is caused by a cell-intrinsic mechanism originating from clonal expansion of eosinophils through acquisition of a somatic mutation, such as FIP1L1-PDGFRA. In recent years, great progress has been made in the field of pathogenesis and molecularly targeted therapy of neoplastic eosinophilia. The diagnostic procedure should include, among other things, morphologic analysis of blood and bone marrow samples, cytogenetics and fluorescence in situ-hybridization tests to detect evidence of an acute or chronic myeloid or lymphoid disorder. Secondary eosinophilia follows a cell-extrinsic mechanism as a response to exogenous cytokines. In most clinical cases, peripheral blood eosinophilia is reactive and typically associated with non-hematological disorders such as infections, allergic conditions, connective tissue disorders, vasculitis, malignancy, or endocrinopathies. Nonetheless, the cause of most cases of hypereosinophilic syndrome remains unknown. In this article, we present a short review focused on differential diagnosis of eosinophilia and eosinophilic disorders. The diagnosis of eosinophilia is a challenge for physicians; thus this review may be useful in clinical practice.

Esophageal cancer is considered one of the most significant challenges to public health worldwide. While various therapeutic options exist for esophageal cancer, including chemotherapy, radiotherapy, and surgery, several adverse effects of these medications have been reported. Therefore, a new generation of therapeutic lines should be applied to minimize complications. In this regard, immunotherapy is a novel approach that aims to kill tumor cells directly by targeting them. Specifically, monoclonal antibodies can target specific markers of esophageal cancer tumor cells, keeping other normal cells safe. Multiple monoclonal antibodies optimized for esophageal cancer, such as pembrolizumab, ramucirumab, trastuzumab, nivolumab, and ipilimumab, are available. On the other hand, esophageal cancer tumor cells express a specific inhibitory ligand and its receptor called programmed cell death, which can suppress T cell immune responses. This receptor provides an inhibitory signal, causing the highest expression of the PD-L1 ligand on tumor cells. The outcomes of this interaction lead to the suppression of the activation and function of T lymphocytes. Therefore, immunotherapy for esophageal cancer targeting the PD-1/PD-L1 pathway has shown a remarkable correlation with cancer care. This study presents a comprehensive review of the latest findings related to immunotherapy in esophageal cancer.

Introduction: Neutrophil autophagy and neutrophil extracellular trap (NET) formation are closely related to asthma pathogenesis. Src homology domain 2-containing protein tyrosine phosphatase 2 (SHP2) is an important regulatory factor in airway remodeling in asthma. This study aimed to explore the molecular mechanisms of SHP2 in neutrophils.

Material and methods: Peripheral blood samples were collected from healthy individuals and asthma patients. A dimethylsulfoxide-induced HL-60-driven neutrophil-like cell model was established. Neutrophil-like cells were treated with rapamycin to activate autophagy. Neutrophil-like cells or neutrophils were transfected with oe-SHP2, si-SHP2, oe-ERK5 or their negative controls.

Results: There was an abnormal increase of neutrophils in the peripheral blood of asthma patients. Neutrophil autophagy gradually decreased with the severity of asthma while the NET formation increased. Pearson's correlation analysis revealed that SHP2 was negatively correlated with BECN1 and LC3 and positively correlated with p62 and MPO. Moreover, SHP2 inhibited autophagy in neutrophil-like cells. Overexpression of ERK5 partially counteracted the inhibitory effect of interfering with SHP2 expression on NET formation in neutrophil-like cells. After interfering with SHP2 expression in neutrophils, the expression of BECN1 and LC3 were significantly increased, while dsDNA levels, MPO activity, and the expression levels of p62, cit-H3, MPO, ELANE, PADI4 and ERK5 were decreased.

Conclusions: Down-regulation of SHP2/ERK5 promoted neutrophil autophagy and inhibited NET formation. SHP2 could be a new indicator of asthma.

Introduction: To explore the effects of anaerobic glycolysis on Jurkat T cell proliferation and clarify the possible mechanism via transcriptomic analysis.

Material and methods: The monocarboxylate transporter 1 inhibitor AZD3965 was used to target and block the transmembrane transport of lactate, thereby inhibiting anaerobic glycolysis in Jurkat T cells. Then, genes with differential expression between treated and untreated cells were detected by transcriptomic analysis, and constructs were generated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses as well as protein-protein interaction (PPI) network analysis were performed to explore the potential mechanism.

Results: Inhibition of anaerobic glycolysis reduced Jurkat T-cell proliferation. RNA sequencing identified 1723 transcripts that were differentially expressed, including 1460 upregulated genes and 263 downregulated genes. GO functional enrichment analysis showed that the differentially expressed genes were mainly involved in the biological processes of response to unfolded protein, response to topologically incorrect protein, and protein folding. KEGG pathway analysis of differentially expressed genes or hub genes from the PPI network analysis revealed enrichment in the estrogen signaling and PI3K-Akt pathways.

Conclusions: Anaerobic glycolysis contributes to the regulation of Jurkat T-cell proliferation. The underlying mechanism may involve the estrogen signaling pathway or PI3K-Akt signaling pathway as well as protein metabolism.

Introduction: Diabetic encephalopathy (DE) is a central nervous complication of type 2 diabetes (T2D). Swertiamarin (SW) is a secoiridoid glycoside reported to have anti-hyperglycemic properties in T2D animal models. Nonetheless, the precise function of SW in T2D-induced DE remains unclarified.

Material and methods: A T2D rat model was established by high-fat diet feeding plus streptozotocin injection, followed by SW administration. Fasting blood glucose and insulin levels were determined. The Morris water maze test was implemented to evaluate rat cognitive function. Hematoxylin-eosin staining was performed for hippocampal morphological observation. Hippocampal p-tau level was detected using immunofluorescence staining. ELISA was utilized to determine inflammatory cytokine production. Western blotting was performed to estimate PI3K/Akt/GSK3 β signaling-related protein levels.

Results: Swertiamarin treatment improved spatial learning and memory and reduced fasting blood glucose as well as insulin levels in T2D rats. SW ameliorated hippocampal morphological changes, reduced tau phosphorylation, and attenuated the inflammatory response in T2D rat hippocampal tissues. SW restored PI3K/Akt/GSK3 β signaling in diabetic rat hippocampus.

Conclusions: Swertiamarin exerts anti-diabetic and anti-inflammatory effects possibly by activating PI3K/Akt/GSK3 β signaling, thereby ameliorating cognitive impairment in T2D rats.

Introduction: Alternative in vitro tests that can be used instead of animal experiments are those that can most closely evaluate the biological activity of the drug of interest. For testing the potency of antivenom, these are the methods used to assess cytotoxicity. The aim of this study was to evaluate the most commonly used cytotoxicity methods for determining the protective potency of the antivenom Viekvin, which neutralizes Vipera ammodytes venom.

Material and methods: The selected methods are based on different biological mechanisms: MTT assay, based on the activity of cell oxidoreductase enzymes; crystal violet staining, based on the degree of cell adhesion; trypan blue staining, based on cell membrane permeability, and propidium iodide staining, based on measurement of nucleic acids of dead cells. The pro-apoptotic effect of the venom was also determined with annexin V staining.

Results: The IC₅₀ value of V. ammodytes venom obtained by these methods was very similar, while the EC₅₀ values differed significantly.

Conclusions: We concluded that the choice of the method used to measure the anticytotoxic anti-venom potency depends on the immunogenicity of the venom components that cause cell death; for each venom/antivenom pair, it is necessary to select the appropriate assay separately, and at present, none of the standard cytotoxic methods can be universally applied to determine antivenom potency.

Introduction: The low-grade inflammation occurring in obese individuals leads to many diseases, including cardiovascular disease (CVD). Dietary patterns, food groups or nutrients in a well-balanced diet may reduce the level of pro-inflammatory markers and the risk of obesity-related morbidities. Our study aims to describe three cytokines in obese patients in relation to dietary habits, lifestyle and body composition.

Material and methods: Serum samples were collected from 84 obese adult volunteer subjects [body mass index (BMI) ≥ 30 kg/m²] to analyze the concentrations of interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ). The subjects were tested by bioelectrical impedance analysis (BIA) and completed a three-day food diary and original questionnaire with the FFQ-6 food consumption frequency questionnaire.

Results and conclusions: Higher serum levels of IL-6 and IFN-γ were found in patients with atherosclerosis, but the group was too small for a reliable correlation. Subcutaneous but not visceral adipose tissue correlated positively with IL-6 levels. Dietary factors such as amount of sugars, including galactose and sucrose, in the diet and the frequency of consumption of sweet flavored dairy products correlated positively with the levels of IL-6 and TNF-α, while the frequency of alcohol consumption negatively correlated with the level of IL-6. The greater the frequency of sports, the higher was the level of IL-6. In obese individuals, the level of pro-inflammatory cytokines could predispose to atherosclerosis and is associated with dietary factors and lifestyle.