Lipocalin-2 Levels Research Articles

Possible involvement of satellite glial cell–derived lipocalin-2 in dermatitis not itch-related behavior of atopic dermatitis model mice

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease with intractable itch. Dorsal root ganglion (DRG) plays an important role in signal transduction of itch. It has been reported that satellite glial cells (SGC) present around DRG neurons are involved in pain and itch through interactions with DRG neurons. However, it is unclear what factors in SGC are involved in inducing dermatitis and itch in DRG. In this study, we found that the expression of lipocalin-2 (LCN2) was increased in SGC of AD model NC/Nga mouse. Therefore, we also examined whether SGC-derived lipocalin-2 is involved in the induction of dermatitis and itch-related behavior in this model mice. Materials and methods: AD-like dermatitis was induced by the application of Dermatophagoides farinae body ointment to NC/Nga mice (AD-NC/Nga mice). Protein and gene expression in the DRG and spinal cord of AD-NC/Nga mice were examined. The effect of the LCN2 antibody on dermatitis pathology in AD-NC/Nga mice was confirmed. Results: LCN2 expression in DRG of AD-NC/Nga mice was higher than that of control NC/Nga mice. Immunohistochemical analysis revealed that LCN2 was expressed on SGC in DRG. Gene expression level of LCN2 in the DRG was significantly increased faster than in the spinal cord during the process of induction of AD-like dermatitis. LCN2 increased gene expression of MMP-9 in mouse DRG. Intrathecally administrated anti-LCN2 antibody twice a week for 3 weeks at the same time as induction of AD-like dermatitis reduced dermatitis score without inhibiting scratching behavior. Discussion: In conclusion, our data suggest that SGC-derived LCN2 is involved in the pathogenesis of dermatitis rather than itch-related behavior in AD-NC/Nga mice.

Inulin protects against the harmful effects of dietary emulsifiers on mice gut microbiome.

The prevalence of inflammatory bowel diseases is increasing, especially in developing countries, with adoption of Western-style diet. This study aimed to investigate the effects of two emulsifiers including lecithin and carboxymethyl cellulose (CMC) on the gut microbiota, intestinal inflammation and the potential of inulin as a means to protect against the harmful effects of emulsifiers. In this study, male C57Bl/6 mice were divided into five groups (n:6/group) (control, CMC, lecithin, CMC+inulin, and lecithin+inulin). Lecithin and CMC were diluted in drinking water (1% w/v) and inulin was administered daily at 5 g/kg for 12 weeks. Histological examination of the ileum and colon, serum IL-10, IL-6, and fecal lipocalin-2 levels were analyzed. 16S rRNA gene V3-V4 region amplicon sequencing was performed on stool samples. In the CMC and lecithin groups, shortening of the villus and a decrease in goblet cells were observed in the ileum and colon, whereas inulin reversed this effect. The lipocalin level, which was 9.7 ±3.29 ng in the CMC group, decreased to 4.1 ±2.98 ng with the administration of inulin. Bifidobacteria and Akkermansia were lower in the CMC group than the control, while they were higher in the CMC+inulin group. In conclusion, emulsifiers affect intestinal health negatively by disrupting the epithelial integrity and altering the composition of the microbiota. Inulin is protective on their harmful effects. In addition, it was found that CMC was more detrimental to microbiota composition than lecithin.

Enhancing cardiometabolic health: unveiling the synergistic effects of high-intensity interval training with spirulina supplementation on selected adipokines, insulin resistance, and anthropometric indices in obese males

This study investigated the combined effects of 12 weeks of high-intensity interval training (HIIT) and spirulina supplementation on adipokine levels, insulin resistance, anthropometric indices, and cardiorespiratory fitness in 44 obese males (aged 25–40 years). The participants were randomly assigned to one of four groups: control (CG), supplement (SG), training (TG), or training plus supplement (TSG). The intervention involved daily administration of either spirulina or a placebo and HIIT three times a week for the training groups. Anthropometric indices, HOMA-IR, VO2peak, and circulating adipokines (asprosin and lipocalin2, omentin-1, irisin, and spexin) were measured before and after the 12-week intervention. Post-intervention analysis indicated differences between the CG and the three interventional groups for body weight, fat-free mass (FFM), percent body fat (%BF), HOMA-IR, and adipokine levels (p < 0.05). TG and SG participants had increased VO2peak (p < 0.05). Spirulina supplementation with HIIT increased VO2peak, omentin-1, irisin, and spexin, while causing decreases in lipocalin-2 and asprosin levels and improvements in body composition (weight, %fat), BMI, and HOMA-IR. Notably, the combination of spirulina and HIIT produced more significant changes in circulating adipokines and cardiometabolic health in obese males compared to either supplementation or HIIT alone (p < 0.05). These findings highlight the synergistic benefits of combining spirulina supplementation with HIIT, showcasing their potential in improving various health parameters and addressing obesity-related concerns in a comprehensive manner.

Serum Lipocalin-2 Levels as a Biomarker in Pre- and Post-Pubertal Klinefelter Syndrome Patients: A Pilot Study.

Klinefelter syndrome (KS) is a male genetic disease caused by the presence of an extra X chromosome, causing endocrine disorders mainly responsible for a high rate of infertility and metabolic disorders in adulthood. Scientific research is interested in identifying new biomarkers that can be predictive or prognostic of alterations strictly connected to KS. Lipocalin-2 (LCN-2, also known as NGAL) is a small protein initially identified within neutrophils as a protein related to innate immunity. Serum LCN-2 estimation seems to be a useful tool in predicting the metabolic complications caused by several pathological conditions. However, little is known about its potential role in infertility conditions. The present pilot study aims to investigate the presence of LCN-2 in the serum of a group of pre-pubertal and post-pubertal children affected by KS, compared to healthy controls. We demonstrated for the first time the presence of elevated levels of LCN-2 in the serum of KS patients, compared to controls. This increase was accompanied, in pre-pubertal KS patients, by the loss of correlation with LH and HDL, which instead was present in the healthy individuals. Moreover, in all KS individuals, a positive correlation between LCN-2 and inhibin B serum concentration was found. Despite the limited size of the sample analyzed, our preliminary data encourage further studies to confirm the findings and to extend the study to KS adult patients, to verify the predictive/prognostic value of LCN-2 as new biomarker for metabolic diseases and infertility associated with the pathology.

Abstract TP300: Apolipoprotein-E Deficiency and High Fat Diet Alter Immunomodulatory Cellular and Molecular Determinants Promoting Atherosclerosis, a Stroke Risk Factor

Background: Most ischemic strokes are caused by atherosclerosis. Atherosclerotic plaque formation is modulated by genetic and environmental interactions. Apolipoprotein E (ApoE) regulates lipid metabolism, and its deficiency is associated with dyslipidemia and atherosclerosis. ApoE is abundantly expressed in glial cells and neurons of the brain, affecting the blood brain barrier and cognitive function. Poor dietary habits promote the onset of atherosclerosis. In this study, we examined the effects of ApoE deficiency and high fat diet (HFD) on plaque formation and immunomodulatory cellular and molecular mechanisms in mice models. Methods: Wild type and ApoE knockout (KO) mice were fed with normal or HFD. Carotid plaques were examined using hematoxylin and eosin staining. Targeted proteomic profiling identified the circulating inflammatory proteins. Pathway specific transcriptomic profiles were identified using PCR arrays and real-time PCR. Immunohistochemistry assays were done in brain sections using a neuronal marker (NeuN), an astrocyte marker (GFAP) and a microglia marker (Iba1). The expression of Pentraxin-3 (PTX3), lipocalin2, and PAI-1 were examined using immunohistochemistry. Images were acquired and analyzed using a Keyence fluorescence microscope and NIH ImageJ. Results: ApoE deficiency and HFD enhanced atherosclerotic plaque formation as a function of age in association with a significant increase in circulating pro-inflammatory cytokines in blood/plasma, including M-CSF, C-reactive protein, and PTX3. The number of microglial cells and astrocytes was increased with altered morphology in ApoE KO and aged animals’ brain cortex and dentate gyrus. Whereas neuronal cell number was decreased in the brains of ApoE deficient and aged mice. The mRNA levels of SELE, PAI-1, lipocalin2, and PTX3 were upregulated in ApoE deficient and WT animals fed with HFD. Higher levels of PTX3 were also observed in atherosclerotic plaques. Conclusion: ApoE deficiency and HFD may play a key role in altering immunomodulatory cellular responses and initiating pro-inflammatory molecular signaling. These events may promote atherosclerotic plaque formation, a risk factor for ischemic stroke and worsen brain damage.

P130 High serum lipocalin-2 expression at the diagnosis in children with ulcerative colitis: a pilot study

Abstract Background The identification of new biomarker is a main challenge in inflammatory boweldisease. Lipocalin-2 (LCN-2) is a pleiotropic mediator of various inflammatory processes. We determined the serum levels of LCN-2 in a cohort of newly diagnosed UC children, and we compared them with healthy controls. Methods Prospective cross-sectional observational study conducted at the Pediatric Gastroenterology, hepatology, and nutrition Unit of the Umberto I Hospital in Rome and at the IBBC – Institute of Biochemistry and Cell Biology – CNR in Rome. All children aged 6-18 years of age, newly diagnosed with UC at the Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, were consecutively enrolled. Blood withdrawal was conducted upon diagnosis. Human serum LCN-2 (Cat. No. DY1757) was measured using a sandwich enzyme-linked-immunosorbent assay (ELISA) kits (R&amp;D Systems, Minneapolis, MN, USA), according to the protocols provided by the manufacturer. Clinical, demographic, biochemical and endoscopic data were recorded. Results Thirty-two children with a new diagnosis of UC [11 (34%) female, mean age 12,7 ± 4] and 38 age- and sex-matched healthy control [21 (55%) females, mean age 11.71 ± 4] were consecutively enrolled. Serum LCN-2 levels were significantly higher in cases compared to controls (280 ± 152 ng/mL vs 66 ± 55 ng/mL), p &amp;lt; 0,001]. Among UC children, significantly higher LCN2 levels were measured in pancolitis (363.7± 155.2 ng/mL) compared to proctitis, left-sided and extensive colitis (184.9 ± 74.65 ng/mL; p = 0.0003). A significant inverse correlation was observed between LCN-2 and albumin levels at the diagnosis by the Spearman coefficient correlation (r = −0.455; P = 0.03) and a significant direct correlation was observed between LCN-2 and CRP values at the diagnosis (r = 0.44; p &amp;lt;0.05). Conclusion Serum LCN-2 levels are significantly higher in children with UC compared to the healthy control group, with the highest levels observed in children with the most extensive disease. Such results as well as and its correlation with the actual disease monitoring tool, make this protein an interesting candidate biomarker.

Intermittent Fasting Reduces Neuroinflammation and Cognitive Impairment in High-Fat Diet-Fed Mice by Downregulating Lipocalin-2 and Galectin-3.

Intermittent fasting (IF), an alternating pattern of dietary restriction, reduces obesity-induced insulin resistance and inflammation. However, the crosstalk between adipose tissue and the hippocampus in diabetic encephalopathy is not fully understood. Here, we investigated the protective effects of IF against neuroinflammation and cognitive impairment in high-fat diet(HFD)-fed mice. Histological analysis revealed that IF reduced crown-like structures and adipocyte apoptosis in the adipose tissue of HFD mice. In addition to circulating lipocalin-2 (LCN2) and galectin-3 (GAL3) levels, IF reduced HFD-induced increases in LCN2- and GAL3-positive macrophages in adipose tissue. IF also improved HFD-induced memory deficits by inhibiting blood-brain barrier breakdown and neuroinflammation. Furthermore, immunofluorescence showed that IF reduced HFD-induced astrocytic LCN2 and microglial GAL3 protein expression in the hippocampus of HFD mice. These findings indicate that HFD-induced adipocyte apoptosis and macrophage infiltration may play a critical role in glial activation and that IF reduces neuroinflammation and cognitive impairment by protecting against blood-brain barrier leakage.

Fluid biomarkers of the neurovascular unit in cerebrovascular disease and vascular cognitive disorders: A systematic review and meta-analysis

BackgroundThe disruption of the neurovascular unit (NVU), which maintains the integrity of the blood brain barrier (BBB), has been identified as a critical mechanism in the development of cerebrovascular and neurodegenerative disorders. However, the understanding of the pathophysiological mechanisms linking NVU dysfunction to the disorders is incomplete, and reliable blood biomarkers to measure NVU dysfunction are yet to be established. This systematic review and meta-analysis aimed to identify biomarkers associated with BBB dysfunction in large vessel disease, small vessel disease (SVD) and vascular cognitive disorders (VCD). MethodsA literature search was conducted in PubMed, EMBASE, Scopus and PsychINFO to identify blood biomarkers related to dysfunction of the NVU in disorders with vascular pathologies published until 20 November 2023. Studies that assayed one or more specific markers in human serum or plasma were included. Quality of studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. Effects were pooled and methodological heterogeneity examined using the random effects model. ResultsA total of 112 studies were included in this review. Where study numbers allowed, biomarkers were analysed using random effect meta-analysis for VCD (1 biomarker; 5 studies) and cerebrovascular disorders, including stroke and SVD (9 biomarkers; 29 studies) while all remaining biomarkers (n = 17 biomarkers; 78 studies) were examined through qualitative analysis. Results of the meta-analysis revealed that cerebrospinal fluid/serum albumin quotient (Q-Alb) reliably differentiates VCD patients from healthy controls (MD = 2.77; 95 % CI = 1.97–3.57; p < 0.0001) while commonly measured biomarkers of endothelial dysfunction (VEGF, VCAM-1, ICAM-1, vWF and E-selectin) and neuronal injury (NfL) were significantly elevated in vascular pathologies. A qualitative assessment of non-meta-analysed biomarkers revealed NSE, NfL, vWF, ICAM-1, VCAM-1, lipocalin-2, MMP-2 and MMP-9 levels to be upregulated in VCD, although these findings were not consistently replicated. ConclusionsThis review identifies several promising biomarkers of NVU dysfunction which require further validation. A panel of biomarkers representing multiple pathophysiological pathways may offer greater discriminative power in distinguishing possible disease mechanisms of VCD.

Lipocalin-2 as a mediator of neuroimmune communication.

Lipocalin-2, a neutrophil gelatinase-associated lipocalin, is a 25-kDa secreted protein implicated in a broad range of inflammatory diseases affecting the brain and periphery. It is a pleotropic protein expressed by various immune and nonimmune cells throughout the body. Importantly, the surge in lipocalin-2 levels in disease states has been associated with a myriad of undesirable effects, further exacerbating the ongoing pathological processes. In the brain, glial cells are the principal source of lipocalin-2, which plays a definitive role in determining their functional phenotypes. In different central nervous system pathologies, an increased expression of glial lipocalin-2 has been linked to neurotoxicity. Lipocalin-2 mediates a crosstalk between central and peripheral immune cells under neuroinflammatory conditions. One intriguing aspect is that elevated lipocalin-2 levels in peripheral disorders, such as cancer, metabolic conditions, and liver diseases, potentially incite an inflammatory activation of glial cells while disrupting neuronal functions. This review comprehensively summarizes the influence of lipocalin-2 on the exacerbation of neuroinflammation by regulating various cellular processes. Additionally, this review explores lipocalin-2 as a mediator of neuroimmune crosstalk in various central nervous system pathologies and highlights the role of lipocalin-2 in carrying inflammatory signals along the neuroimmune axis.

Altered IL-3 and lipocalin-2 levels are associated with the pathophysiology of major depressive disorder: a case-control study

BackgroundMajor Depressive Disorder (MDD) is a common mental ailment and is the primary reason for disability. It manifests a severe impact on moods, thoughts, and physical health. At present, this disorder has become a concern in the field of public health. Alteration of neurochemicals is thought to be involved in the pathogenesis of many psychiatric disorders. Therefore, we aimed to evaluate serum IL-3 and lipocalin-2 in MDD patients and healthy controls (HCs).MethodWe included a total of 376 participants in this study. Among them, 196 were MDD patients, and 180 were age-sex-matched HCs. MDD patients were recruited from the Psychiatry Department of Bangabandhu Sheikh Mujib Medical University (BSMMU), but the controls were from different parts of Dhaka. All study participants were evaluated by a psychiatrist using the DSM-5 criteria. To assess the severity of the depression, we used the Hamilton depression (Ham-D) rating scale. Serum IL-3 and lipocalin-2 levels were measured using commercially available enzyme-linked immune-sorbent assay kits (ELISA kits).ResultsAccording to this study, we observed elevated serum levels of IL-3 (1,024.73 ± 29.84 pg/mL) and reduced levels of serum lipocalin-2 (29.019 ± 2.073 ng/mL) in MDD patients compared to HCs (911.11 ± 20.55 pg/mL and 48.065 ± 3.583 ng/mL, respectively). No associations between serum levels of IL-3 and lipocalin-2 and depression severity were observed in patients.ConclusionsAccording to the present findings, alterations of serum IL-3 and lipocalin might be associated with the pathogenesis of MDD. These results support that altered serum neurochemicals can serve as early risk assessment markers for depression. Further interventional studies are recommended for a better understanding of the role of IL-3 and lipocalin-2 in the pathophysiology of depression.

Hemorrhagic Fever with Renal Syndrome Patients Exhibit Increased Levels of Lipocalin-2, Endothelin-1 and NT-proBNP.

Hemorrhagic fever with renal syndrome (HFRS) is an acute zoonotic disease caused by viruses of the Orthohantavirus genus. This syndrome is characterized by renal and cardiopulmonary implications detectable with different biomarkers. Here, we explored the role of serum and urine levels of lipocalin-2, endothelin-1 and N-terminal pro-brain natriuretic peptide (NT-proBNP) in HFRS pathology. A total of twenty-eight patients hospitalized due to a Puumala orthohantavirus infection were included, with serum and urine samples collected on patient admission (acute phase) and discharge (convalescent phase). In comparison to healthy individuals, patients exhibited significantly higher acute-phase serum and urine levels of lipocalin-2, serum levels of endothelin-1 and serum and urine levels of NT-proBNP. Patients in the convalescent phase showed a significant decrease in urine lipocalin-2, serum endothelin-1 and serum and urine NT-proBNP levels. We recorded a strong correlation between serum levels of lipocalin-2 and endothelin-1 and urine levels of lipocalin-2 with several kidney injury markers, such as serum creatinine, urea, urine white blood cell count and proteinuria. We also demonstrated an independent correlation of serum and urine lipocalin-2 levels with acute kidney injury in HFRS. All in all, our results show an involvement of NT-proBNP, lipocalin-2 and endothelin-1 in the renal and cardiac pathology of HFRS.

Hydrogen gas and the gut microbiota are potential biomarkers for the development of experimental colitis in mice.

Inflammatory bowel disease (IBD) is a chronic disease characterised by repeated relapses and remissions and a high recurrence rate even after symptom resolution. The primary method for IBD diagnosis is endoscopy; however, this method is expensive, invasive, and cumbersome to use serially. Therefore, more convenient and non-invasive methods for IBD diagnosis are needed. In this study, we aimed to identify biological gas markers for the development of gut inflammation. Using dextran sulphate sodium (DSS)-induced colitis mouse models, five biological gases were analysed to identify predictive markers for the development of gut inflammation. Additionally, the correlation between the changes in gas composition, gut microbiota, and inflammatory markers was assessed. The hydrogen (H2) level was found to be negatively correlated with the level of lipocalin-2 (LCN2), a gut inflammation biomarker, and weight loss due to DSS-induced colitis. Furthermore, gut microbes belonging to the Rikenellaceae and Akkermansiaceae families were positively correlated with LCN2 levels and weight loss, whereas Tannerellaceae abundance was negatively correlated with LCN2 level and weight loss and positively correlated with H2 levels. This study provides new insights for IBD diagnosis; the H2 levels in biological gases are a potential biomarker for intestinal inflammation, and specific gut microbes are associated with H2 level changes.

Dynamics of iron metabolism in patients with bloodstream infections: a time-course clinical study

The close relationship between infectious diseases and iron metabolism is well known, but a more detailed understanding based on current knowledge may provide new insights into the diagnosis and treatment of infectious diseases, considering the growing threat of antibiotic-resistant bacteria. This study investigated adult patients with bloodstream infections, temporal changes, and relationships between blood levels of iron and related markers, including hepcidin and lipocalin-2 (LCN2). We included 144 samples from 48 patients (mean age 72 years, 50% male), with 30 diagnosed with sepsis. During the acute phase of infection, blood levels of hepcidin and LCN2 increased rapidly, whereas iron levels decreased, with values in 95.8% of cases below the normal range (40–188 μg/dL). Later, hepcidin and LCN2 decreased significantly during the recovery phase, and the decreased iron concentrations were restored. In the case of persistent inflammation, iron remained decreased. Acute LCN2 levels were significantly higher in patients with sepsis (p < 0.01). Hypoferremia induced by increased hepcidin would reduce iron in the environment of extracellular pathogens, and the increased LCN2 would inhibit siderophores, resulting in the prevention of the pathogen’s iron acquisition in each manner during the acute phase of bloodstream infection.

NR3C2 activates LCN2 transcription to promote endoplasmic reticulum stress and cell apoptosis in ischemic cerebral infarction

Endoplasmic reticulum (ER) stress can lead to cell death and worsen tissue damage during ischemic events. Nuclear receptor subfamily 3 group C member 2 (NR3C2) and lipocalin 2 (LCN2) are known to be associated with ER stress. In this study, we obtained a potential interaction between NR3C2 and LCN2 through bioinformatics. The primary objective was to investigate their roles and interactions in the context of ER stress in ischemic cerebral infarction (ICI). A mouse model of ICI was generated by middle cerebral artery occlusion, resulting in elevated levels of NR3C2 and LCN2 in brain tissues. NR3C2 bound to the LCN2 promoter, thereby activating its transcription. Either knockdown of LCN2 or NR3C2 led to an improvement in neurologic deficits in mice, along with a reduction in infract size, tissue damage, ER stress, inflammation, and cell apoptosis in their brain tissues. Similar results were reproduced in HT22 cells, where LCN2 or NR3C2 knockdown alleviated oxygen-glucose deprivation-induced ER stress, inflammation, and cell apoptosis while improving cell viability. However, the protective effects of NR3C2 knockdown were counteracted when LCN2 was overexpressed, both in vitro and in vivo. Overall, this study demonstrates that NR3C2 activates LCN2 transcription, ultimately promoting ER stress and cell apoptosis in the context of ICI.

Circulating Levels of Leptin and Lipocalin-2 in Patients With X-Linked Hypophosphatemia.

Individuals with X-linked hypophosphatemia (XLH) are at greater risk for being overweight or obese. Whether there are underlying metabolic abnormalities that put patients with XLH at greater risk for excessive weight gain is largely unknown. Lipocalin-2 (LCN2) has recently received attention as a factor regulating energy consumption and specifically is postulated to be anorexigenic and to improve insulin sensitivity. In a retrospective study, circulating levels of LCN2, leptin, and insulin were measured in 32 patients with XLH, ages 2-60 years, all of whom were being treated with burosumab, and 38 control subjects. Control subjects were chosen who were close in age to those with XLH, with a similar number of participants of each sex. Subjects were analyzed in 3 age cohorts, 2-10 years, 11-18 years, and 20-60 years. In all age groups LCN2 levels were lower in the patients with XLH than in controls but when adjusted for weight class (normal, overweight, obese) the differences were not significant. In contrast, serum leptin levels were significantly lower in children with XLH compared to controls in the 2-10 years age cohort. Serum levels of insulin were also significantly lower in the 2-10-year-old children with XLH when compared with controls. We conclude that changes in expression of lipocalin-2 in children and adolescents with XLH is unlikely to contribute to their risk for obesity in adulthood. It is unclear if lower circulating levels of leptin in these children plays a role in the higher prevalence of obesity among adults with XLH.

The contribution of IL-17A-dependent low LCN2 levels to Helicobacter pylori infection: Insights from clinical and experimental studies

BackgroundHelicobacter pylori (H. pylori) infection is a common bacterial infection that is widespread globally. It is crucial to comprehend the molecular mechanisms that underlie the infection caused by H. pylori in order to devise successful therapeutic approaches. The objective of this study was to examine the involvement of Lipocalin-2 (LCN2) in the development of H. pylori infection. MethodsLCN2 expression levels in human gastric mucosa and H. pylori-infected mouse models were analyzed using quantitative PCR and immunohistochemistry methods. The effects of LCN2 on the attachment of H. pylori to gastric mucosa cells were assessed using bacterial culture and fluorescence intensity tests. To investigate the correlation between LCN2, CCL20, and IL-17A, we performed gene expression analysis and measured serum levels. ResultsThe findings indicated an increase in LCN2 levels in the gastric mucosa of both patients and mice infected with H. pylori. Blocking the natural LCN2 resulted in an increased attachment of H. pylori to cells in the gastric mucosa. In addition, we noticed that reduced levels of LCN2 promoted the attachment of H. pylori to cells in the gastric mucosa. Furthermore, H. pylori-infected patients exhibited increased expression of both LCN2 and CCL20, and there was a positive correlation between serum levels of CCL20 and LCN2. LCN2 expression was found to depend on the presence of IL-17A, and inhibiting IL-17A led to a higher H. pylori colonization. ConclusionThe persistence of H. pylori infection is facilitated by the presence of low levels of LCN2, which is dependent on IL-17A. This finding offers valuable perspectives for the development of novel therapeutic approaches for H. pylori infection.

Serum and Tissue Lipocalin-2 Expression in Chronic Kidney Disease Pruritic Patients.

Uremic pruritus is an irritating symptom for patients with end-stage kidney disease. Lipocalin-2 (LCN2) has relevant importance in several biological cellular processes and immunity. It is also a major player in the progression of many disorders, such as renal injury. To evaluate LCN2 expression in chronic kidney disease (CKD) pruritic patients in serum together with immunohistochemical expression in skin samples and further correlation of their results with the studied clinicopathologic parameters. Serum level of LCN2 (assessed by enzyme-linked immunosorbent assay) and skin immunohistochemical expression were investigated in 25 CKD patients and 25 healthy controls. Ten patients were subjected to narrowband ultraviolet B phototherapy for 12 weeks then re-evaluated for serum and tissue LCN2 after therapy. LCN2 expression was increased significantly in both the epidermis and dermal adnexa in CKD patients over controls. Also, serum LCN2 level was higher in patients than in healthy subjects and was significantly associated with itching severity, grades of CKD, urea, and creatinine serum level. Tissue and serum levels of LCN2 were significantly diminished in CKD patients following narrowband therapy along with improvement of the severity of pruritus. The increased serum and tissue LCN2 expression in CKD pruritic patients and its pronounced decrease, in addition to the improvement of pruritus after treatment, suggest a major pathogenic role of LCN2 in uremic pruritus.

Abstract 003: Aberrant Host Immune Responses Specific To Microbial-derived Ligands Are Linked To Hypertension In BPH/2J Mice

It has been established that derangements in host-microbiota homeostasis leads to hypertension. However, the precise mechanisms remain largely unknown. Microbial-derived ligands released into the host circulation are sensed and eliminated by various host innate and adaptive immune mechanisms. Herein, we focused on such microbial-derived ligands and hypothesized that defect in host innate and adaptive immune response to counter microbial-derived ligands is linked to hypertension. To test this hypothesis, both in vitro and in vivo studies were conducted. First, bone marrow-derived macrophages from Blood Pressure Normal (BPN/3J, systolic blood pressure: 113.2±2.20 mm Hg) and Blood Pressure Hypertensive (BPH/2J, systolic blood pressure: 143.9±4.10 mm Hg) mice (male, 8 weeks) were challenged with various Toll-like receptor (TLR) ligands of microbial origin. Unstimulated macrophages from BPH mice displayed reduced levels of the co-stimulatory activation markers CD40, CD80 and CD86 (~2 fold) compared to macrophages from BPN/3J mice. Such differences, however, was normalized upon stimulation with ligands for TLR3 (poly-I:C), TLR4 (LPS), TLR5 (flagellin), TLR7/8 (R848) and TLR9 (CpG-DNA). Despite so, BPH-macrophages displayed blunted IL-6 and lipocalin-2 (~2 fold) levels in response to all the aforementioned TLR ligands when compared to macrophages from BPN mice. To confirm these findings in vivo , we challenged BPN and BPH mice with the microbial-derived ligand, flagellin. Interestingly, even though BPH mice had reduced cytokine responses to flagellin as monitored by levels of Lcn2 (BPN 320.9 ± 22.20 vs BPH 230.8 ± 12.40, p&lt;0.05) and CXCL1 (BPN 40.9 ± 4.6 vs BPH 23.8 ± 2.4, p&lt;0.05), they displayed higher levels of flagellin-specific IgG (BPN vs BPH O.D 450 , 0.51 ± 0.10 vs 0.93 ± 0.07, p&lt;0.05) and substantially lower levels of flagellin-specific IgA (BPN vs BPH O.D 450 , 0.44 ± 0.13 v s 0.13 ± 0.03, p&lt;0.05). Collectively, both in vitro and in vivo studies demonstrate that both innate and adaptive immune responses specifically against microbial ligands is substantially deranged in the hypertensive state.

Evaluation of Serum Lipocalin-2 Level and Its Relation to Insulin Resistance in Patients with Inflammatory Acne Vulgaris

Abstract Introduction Acne vulgaris is a common chronic inflammatory disease of the pilosebaceous unit. It is characterized by the formation of non-inflammatory comedones and inflammatory papules, pustules, nodules and cysts. Lipocalin-2 (LCN2) is an attractive biomarker of inflammation, ischemia, infection, and kidney damage. Aim of the Study The current study aimed to evaluate serum Lipocalin-2 levels in inflammatory acne vulgaris patients and to reveal the possible relation between its serum levels and the insulin resistance status in acne patients. Patients and Methods The study included 60 patients suffering from inflammatory acne vulgaris and 60 healthy control subjects. Full general and dermatological examination were performed, recording of BMI, GAGS score was done. Then, measurement of fasting insulin and fasting glucose was performed to calculate HOMA-IR. Results Serum lipocalin-2, fasting insulin and HOMA-IR levels were significantly higher in acne patients compared to control subjects. Conclusion Inflammatory acne vulgaris patients have higher levels of serum lipocalin-2 which might be related to acne pathogenesis.

Lipocalin-2 promotes neutrophilic inflammation in nasal polyps and its value as biomarker

BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is a common chronic inflammatory disease of the nasal cavity and paranasal sinuses. The role of neutrophils in the pathogenesis of CRSwNP has attracted more attention in recent years, due to its association with more severe disease and reduced steroid responsiveness. Lipocalin-2 (LCN2) has been found to modulate neutrophils infiltration in other neutrophilic inflammation including inflammatory bowel disease, rheumatoid arthritis, and psoriasis. The aim was to evaluate the expression and regulator role of LCN2 in neutrophilic inflammation in CRSwNP, and its role as a potential biomarker predicting non-eosinophilic CRSwNP (neCRSwNP). MethodsBioinformatic analysis, immunostainings, real-time PCR and ELISA were used to analyze the expression and location of LCN2 in nasal tissues. The expression of proinflammatory mediators were assessed in nasal tissues and secretions. LCN2 production in human nasal epithelial cells (HNECs) and neutrophils, as well as its role in neutrophilic inflammation was evaluated by in vitro experiments. ResultsLCN2 was mainly located in neutrophils and HNECs of nasal polyps. LCN2 expression was also significantly higher in the polyp tissue and nasal secretions from patients with neCRSwNP. The LCN2 levels were positively correlated with type 3 inflammation markers, including G-CSF, IL-8, and IL-17. LCN2 expression could be upregulated by IL-17 A and TNF-α in HNECs, and LCN2 could also promote the expression of IL-8 in dispersed polyp cells and HNECs. ConclusionsLCN2 could serve as a novel biomarker predicting patients with neCRSwNP, and the increased expression of LCN2 may participate in the pathogenesis of neCRSwNP.