Serum Lipocalin-2 Concentrations Research Articles

Perinatal lipocalin-2 profile at the extremes of fetal growth

Background Lipocalin-2 (LCN-2) has been identified as an osteoblast-secreted hormone regulating immunity, inflammation and metabolic homeostasis and has emerged as a diagnostic and prognostic biomarker for acute kidney injury in neonates. We investigated the impact of fetal growth on antepartum maternal serum, cord serum and breast milk LCN-2 concentrations and the associations of the latter with perinatal parameters. Methods Maternal serum, cord serum and breast milk LCN-2 concentrations were measured by ELISA in samples from 80 mothers who delivered 40 appropriate (AGA), 20 large for gestational age (LGA) and 20 intrauterine growth restricted (IUGR) neonates, classified by customized weight centiles. LCN-2 concentrations were associated with birth weight, customized centile, gender, maternal age and delivery mode. Results Antepartum maternal serum LCN-2 concentrations were significantly higher in women delivering AGA infants compared to the other two groups. Cord blood LCN-2 concentrations were significantly higher compared to maternal ones; furthermore, they were significantly elevated in the IUGR group compared to the LGA one (p = .019). Lowest concentrations were detected in breast milk, which did not differ between the three growth groups. A negative correlation was documented between cord blood LCN-2 concentrations and customized centiles (r: −0.304, p = .007). Conclusions The higher cord serum LCN-2 concentrations, compared to maternal ones, may point to its fetal origin and potential role in intrauterine growth. The negative correlation of cord LCN-2 concentrations with customized centiles, possibly implies reduced nephron endowment/subclinical kidney damage in IUGR neonates. The extremely low LCN-2 breast milk concentrations could imply that the secretion of LCN-2 from maternal circulation to breast milk is not influenced by factors leading to intrauterine growth pathology.

Association of Serum Lipocalin-2 Concentrations with Psoriasis and Psoriatic Arthritis: An Updated Meta-Analysis.

Objectives The purpose of this study was to explore the association of serum lipocalin-2 concentrations with psoriasis and psoriatic arthritis (PsA). Methods A systematic search of studies on the association of serum lipocalin-2 concentrations with psoriasis/PsA was conducted in PubMed, Web of Science, Elsevier ScienceDirect, and Cochrane Library. Eventually, 8 eligible studies were included. The strength of association between serum lipocalin-2 concentrations and psoriasis/PsA was assessed by pooled standard mean difference (SMD) with its 95% confidence intervals (CIs). Results A total of 8 case-control studies, consisting of 349 psoriasis/PsA patients and 258 controls, were included in the meta-analysis. This meta-analysis showed significant association between serum lipocalin-2 concentrations and psoriasis/PsA in overall population (SMD: 0.757, 95%CI = 0.588‐0.926, and PH = 0.114; PH is the P value for the heterogeneity test). Similar results were found in subgroup analysis by ethnicity. Conclusions Serum lipocalin-2 concentrations are higher in psoriasis/PsA patients than controls. However, more large-scale studies are warranted to explore the association between serum lipocalin-2 and the pathogenetic mechanisms of psoriasis/PsA.

Relationship between the Degrees of Itch and Serum Lipocalin-2 Levels in Patients with Psoriasis.

Background Lipocalin-2 (LCN2), a protein secreted mainly by activated neutrophils, has been associated with neurodegeneration, obesity, and inflammatory responses. Serum LCN2 concentration has been reported elevated in patients with psoriasis, but lower in patients with atopic dermatitis (AD). Spinal astrocyte-derived LCN2 was found to be involved in enhancement of itch in a mouse model of AD. However, the relationship between LCN2 and itch in patients with psoriasis has not been determined. Objective. This study examined the correlation between serum LCN2 levels and the degrees of itch in patients with psoriasis. Methods Serum LCN2 concentrations were measured by enzyme-linked immunosorbent assays (ELISA) in patients with psoriasis and AD and in healthy controls. The degree of itch was assessed using a visual analog scale (VAS), and disease severity was determined by measuring psoriasis area and severity index (PASI) and scoring atopic dermatitis (SCORAD). Correlations among serum LCN2 level, VAS, PASI, and SCORAD were analyzed statistically. We further examined the serum LCN levels in psoriasis patients before and after biological treatment. Results Serum LCN2 concentrations were significantly higher in patients with psoriasis and AD than those in healthy controls. In patients with psoriasis, serum LCN2 concentrations were significantly correlated with VAS, but not with PASI. In contrast, serum LCN2 concentrations did not correlate with VAS or SCORAD in patients with AD. Serum LCN2 levels in psoriasis patients significantly decreased after the biological treatment along with improvement of VAS. Conclusion Serum LCN2 concentration is associated with the degree of itch in patients with psoriasis, suggesting that serum LCN2 may be a useful clinical marker for itch in psoriasis.

Clinical efficacy of sublingual immunotherapy is associated with restoration of steady-state serum lipocalin 2 after SLIT: a pilot study

Background So far, only a few biomarkers in allergen immunotherapy exist that are associated with a clinical benefit. We thus investigated in a pilot study whether innate molecules such as the molecule lipocalin-2 (LCN2), with implications in immune tolerance demonstrated in other fields, may discriminate A) between allergic and non-allergic individuals, and B) between patients clinically responding or non-responding to sublingual allergen immunotherapy (SLIT) with house dust mite (HDM) extract. Moreover, we assessed haematological changes potentially correlating with allergic symptoms.Methods LCN2-concentrations were assessed in sera of healthy and allergic subjects (n = 126) as well as of house dust mite (HDM) allergics before and during HDM- sublingual immunotherapy (SLIT) in a randomized, double-blind, placebo-controlled trial for 24 weeks. Sera pre-SLIT (week 0), post-SLIT (week 24) and 9 months after SLIT were assessed for LCN2 levels and correlated with total nasal symptom scores (TNSS) obtained during chamber challenge at week 24 in patients receiving HDM- (n = 31) or placebo-SLIT (n = 10).Results Allergic individuals had significantly (p < 0.0001) lower LCN2-levels than healthy controls. HDM-allergic patients who received HDM-SLIT showed a significant increase in LCN2 9 months after termination of HDM-SLIT (p < 0.001), whereas in subjects receiving placebo no increase in LCN2 was observed. Among blood parameters a lower absolute rise in the lymphocyte population (p < 0.05) negatively correlated with symptom improvement (Pearson r 0.3395), and a lower relative increase in the neutrophils were associated with improvement in TNSS (p < 0.05). LCN2 levels 9 months after immunotherapy showed a low positive correlation with the relative improvement of symptoms (Pearson r 0.3293). LCN2-levels 9 months off-SLIT were significantly higher in patients whose symptoms improved during chamber challenge than in those whose symptoms aggravated (p < 0.01).Conclusion Serum LCN2 concentrations 9 months off-SLIT correlated with clinical reactivity in allergic patients. An increase in the LCN2 levels 9 months after HDM-SLIT was associated with a clinical benefit. Serum LCN2 may thus contribute to assess clinical reactivity in allergic patients.Trial registration Part of the data were generated from clinicaltrials.gov Identifier NCT01644617.

Serum lipocalin-2 concentrations and mortality of severe traumatic brain injury

BackgroundLipocalin-2 is related to acute brain injury. We assessed the prognostic value of serum lipocalin-2 in head trauma. MethodsBlood samples were collected from 115 controls and 115 patients with severe traumatic brain injury. Trauma severity was assessed by Glasgow Coma Scale (GCS) scores at baseline. Thirty-day mortality and overall survival time were recorded. ResultsCompared with the controls, serum lipocalin-2 concentrations were significantly increased in the patients. Lipocalin-2 concentrations were independently associated with GCS scores (t=−7.271, P<0.001) and serum C-reactive protein concentrations (t=4.325, P<0.001). Under receiver operating characteristic curve for 30-day mortality, sensitivity and specificity were 85.7% and 63.2% respectively for lipocalin-2 concentrations at a cutoff value of 591ng/ml. Additionally, area under curve (AUC) of lipocalin-2 concentrations [AUC, 0.825; 95% confidence interval (95% CI), 0.743–0.889] was equivalent to that of GCS scores (AUC, 0.869; 95% CI, 0.793–0.925; P=0.413). Moreover, serum lipocalin-2 concentrations >591ng/ml emerged as an independent predictor for 30-day mortality (odds ratio, 4.360; 95% CI, 1.908–12.430) and overall survival (hazard ratio, 3.820; 95% CI, 1.935–10.500). ConclusionsEnhanced serum concentration of lipocalin-2 at admission is associated with trauma severity and neuroinflammation as well as is a predictor of mortality after head trauma.

Lipocalin-2 expression and serum levels as early predictors of type 2 diabetes mellitus in obese women.

Obesity and diabetes are increasing in epidemic proportions globally. Lipocalin-2 (LCN-2) is an inflammatory adipocytokine and obesity-related marker of low-grade inflammation. We aimed to investigate, for first time, the possible role of LCN-2 expression and serum levels in prediction of impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) among obese Egyptian women. This study included 188 obese women and 180 controls. Obese women were subdivided into three subgroups according to their fasting blood glucose, normal glucose tolerance (NGT), IGT and T2DM. Circulating LCN-2 expression levels were determined by real time polymerase chain reaction. Serum LCN-2 concentrations were assessed by ELISA. Our findings revealed that LCN-2 expression and serum levels were higher in obese women compared to lean controls. They were higher in IGT and T2DM obese cases than in NGT obese women. Receiver operating characteristic analyses revealed that LCN-2 expression level was a useful biomarker discriminating IGT from NGT and T2DM from IGT obese women (AUC were 0.735 and 0.740, respectively). It was an independent predictor of IGT and T2DM among obese women. Serum LCN-2 level was a useful biomarker discriminating IGT from NGT and T2DM from IGT obese women (AUC were 0.705 and 0.728, respectively). It was independent predictor of T2DM without predicting IGT among obese women. The power of combined LCN-2 serum levels and expression in discriminating between IGT from NGT and T2DM from IGT obese women was high (AUC = 0.717 and 0.741, respectively). In conclusion, LCN-2 expression and serum levels could discriminate IGT from NGT and T2DM from IGT obese women and early predicting T2DM among obese women. While, LCN-2 expression level was the independent predictor of IGT in obese women. Combination of both LCN-2 expression and serum levels improved their diagnostic value in early detection of IGT and T2DM among obese women. © 2017 IUBMB Life, 69(2):88-97, 2017.

Effect of psoriasis activity and topical treatment on serum lipocalin-2 levels

Objective: Psoriasis has been considered as systemic disorder. Lipocalin-2 might be a link between psoriasis and its comorbidities. Aim of the study was to investigate the associations between serum lipocalin-2 levels and the disease activity, markers of inflammation or metabolic disturbances and changes after topical treatment in psoriatic patients. Methods: Thirty-seven individuals with active plaque-type psoriasis and 15 healthy controls were recruited. Blood samples were collected before and after 14 days of therapy. Serum lipocalin-2 concentrations were examined by enzyme-linked immunosorbent assay. The results were correlated with Psoriasis Area and Severity Index (PASI), body mass index (BMI), inflammatory and biochemical markers, lipid profile and with effectiveness of topical treatment.Results: Lipocalin-2 serum levels were significantly increased in psoriatic patients in comparison to the controls (p = 0.023). No significant correlations with indicators of inflammation, nor BMI or PASI were noted. A statistical association between lipocalin-2 and low-density lipoprotein-cholesterol was shown. After topical treatment serum lipocalin-2 level did not significantly change (p = 0.9), still remaining higher than in the controls, despite clinical improvement.Conclusions: Lipocalin-2 might be a marker of psoriasis and convey cardiovascular or metabolic risk in psoriatic patients, but may not be a reliable indicator of inflammation, severity of psoriasis nor efficacy of antipsoriatic treatment.

Serum Lipocalin 2 Levels in Acute Exercised Prediabetic Rat Model in Comparison to Normal Healthy Control

Background: Excess caloric intake expands adipose tissue resulting in a higher risk of metabolic disease. Lipocalin 2 (LCN2) is an adipokine having a role in innate immunity and energy metabolism. It is an acute phase protein that was recently correlated with potential effects on obesity and inflammation. The reaction of this protein to progressive exercise in animals has limited studies. Exercise encourages weight loss and improves insulin sympathy. However, the molecular mechanisms mediating its beneficial effects are not fully understood. Obesity associates with increased production of inflammatory cytokines, which in turn, subsidizes to systemic insulin resistance. LCN2 has been shown to have a significant association with body mass index (BMI). However, only few of the LCN2-related studies have investigated whether LCN2 constitutes a causal factor of the metabolic conditions in animals. One of the best strategies to prevent obesity and its associated inflammation is participation in regular physical activity. Objective: This study was designed to test the hypothesis that exercise mitigates this inflammatory response, thereby improving insulin sensitivity, we tested whether there is an insulin-sensitizing effect of exercise is associated with related changes in circulating LCN2 levels in rats. Design: A total number of 24 adult healthy male albino rats were used. Rats were divided into three groups: group I (control, C), group II (model of pre-diabetic obese rats without exercise, PD) and group III (model of pre-diabetic obese rats with acute voluntary exercise, PDE). Results: This study revealed that after a 2 days acute exercise program, insulin sensitivity was improved, as indicated by a significant decrease in serum insulin (1.98±0.04), serum glucose (121.75±2.85) and Homeostasis Model Assessment for Insulin Resistance Index (HOMA-IR) (0.59±0.02) in PDE in comparison to corresponding values in PD group (3.94±0.08), (159±1.49) and (1.44±0.11) respectively. Also, Serum LCN2 concentrations were significantly decreased (62.88±1.79) in PDE group in comparison to PD group (94.75±3.36). Conclusion: We concluded that exercise has an insulin sensitizing effect in the pre-diabetic stage and its mechanism could involve a reduction in LCN2 levels in exercise-trained group.

Lipocalin-2 Serum Levels Are Increased in Acute Hepatic Failure

Lipocalin-2 (LCN-2), which is expressed in immunocytes as well as hepatocytes, is upregulated in cells under stress from infection or inflammation with increase in serum levels. We sought to investigate the relevance of LCN-2 in the setting of acute hepatic failure, particularly when addressed with the molecular adsorbent recirculating system (MARS). We measured serum LCN-2 concentrations with enzyme-linked immunosorbent assay (ELISA) in 8 patients with acute-on-chronic-liver failure (ACLF) and acute liver failure (ALF) who were treated with MARS. The controls were 14 patients with stable chronic hepatic failure (CHF). LCN-2 was determined immediately before and after the first MARS session. Baseline LCN-2 serum concentrations were significantly increased among ACLF and ALF patients as compared with CHF (P = .004 and P = .0086, respectively). There was no significant difference between the ALF and ACLF group. Moreover, serum LCN-2 levels did not change significantly during the MARS treatment. Serum LCN-2 levels, therefore, may be useful to discern acute from chronic hepatic failure and to monitor the course as well as the severity of the disease.

LIPOCALIN-2 Is a Major Acute-Phase Protein in a Rat and Mouse Model of Sterile Abscess

Lipocalin-2 (LCN-2) is a 25-kDa secretory protein currently used as a biomarker for renal injury and inflammation. Its source and cause of the increased serum levels are unclear. The current study compares LCN-2 gene expression with known major acute-phase proteins in the liver in a rat and mouse model of turpentine oil-induced sterile abscess. Serum LCN-2 concentrations increased dramatically up to 200-fold (20 μg/mL) at 48 h after turpentine oil injection. A strong elevation of LCN-2 mRNA in rat liver was observed starting from 4 h up to 48 h after injection, with a maximum (8,738 ± 2,104-fold) at 24 h, which was further confirmed by Western blot analysis. In contrast, the increases in gene expression of α₂-macroglobulin, the major acute-phase protein, and hemoxygenase 1, a positive acute-phase protein, were only 1,025 ± 505-fold and 47 ± 12-fold, respectively, during acute-phase reaction (APR). No considerable change was observed in LCN-2 mRNA in rat kidney and other organs as compared with liver. Using wild-type mice, a massive increase in gene expression of LCN-2, with a maximum of 2,498 ± 84-fold in liver, which is similar to that for serum amyloid A (2,825 ± 233-fold), a major mouse acute-phase protein. However, such an increase was significantly inhibited in interleukin 6 knockout mice during APR. Interleukin 6-treated rat hepatocytes induced a significant time-dependent upregulation of LCN-2.Lipocalin-2 is the major acute-phase protein in rat as compared with α₂-macroglobulin and hemoxygenase 1 and comparable with serum amyloid A in mouse whose gene expression is mainly controlled by interleukin 6. The liver is the main source of serum LCN-2 in the case of APR. ABBREVIATIONS-LCN-2-lipocalin-2-α₂M-α₂-macroglobulin-HO-1-hemoxygenase 1-IL-6-interleukin 6-SAA-serum amyloid A-TO-turpentine oil-APR-acute-phase reaction.

Lipocalin-2 Is an Inflammatory Marker Closely Associated with Obesity, Insulin Resistance, and Hyperglycemia in Humans

Lipocalin-2, a 25-kDa secreted glycoprotein, is a useful biomarker for early detection of various renal injuries. Because lipocalin-2 is abundantly expressed in adipose tissue and liver, we investigated its relevance to obesity-related pathologies. We used real-time PCR and in-house immunoassays to quantify the mRNA and serum concentrations of lipocalin-2 in C57BL/KsJ db/db obese mice and their age- and sex-matched lean littermates. We analyzed the association between serum lipocalin-2 concentrations and various metabolic and inflammatory variables in 229 persons (121 men and 108 women) recruited from a previous cross-sectional study, and we evaluated the effect of the insulin-sensitizing drug rosiglitazone on serum lipocalin-2 concentrations in 32 diabetic patients (21 men and 11 women). Compared with the lean littermates, lipocalin-2 mRNA expression in adipose tissue and liver and its circulating concentrations were significantly increased in db/db diabetic/obese mice (P <0.001). These changes were normalized after rosiglitazone treatment. In humans, circulating lipocalin-2 concentrations were positively correlated (P <0.005) with adiposity, hypertriglyceridemia, hyperglycemia, and the insulin resistance index, but negatively correlated (P = 0.002) with HDL cholesterol. There was also a strong positive association between lipocalin-2 concentrations and high sensitivity C-reactive protein (hs-CRP), independent of age, sex, and adiposity (P = 0.007). Furthermore, rosiglitazone-mediated decreases in lipocalin-2 concentrations correlated significantly with increases in insulin sensitivity (r = 0.527; P = 0.002) and decreases in hs-CRP concentrations (r = 0.509; P = 0.003). Lipocalin-2 is an inflammatory marker closely related to obesity and its metabolic complications. Measurement of serum lipocalin-2 might be useful for evaluating the outcomes of various clinical interventions for obesity-related metabolic and cardiovascular diseases.