Interleukin-1β as a driver of renal NGAL production

Bonnemaison, Mathilde L.; Marks, Eileen; Boesen, Erika I.

doi:10.1016/j.cyto.2016.12.004

Cited by 16 publications

(12 citation statements)

References 46 publications

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“…It is also interesting to note that the identified immunological markers interact with each other during urological infection by restricting bacterial growth and mediating trans-epithelial movement of neutrophils 36 . IL-1β induces renal production of NGAL in mice model experiments 37 , and NGAL modulates MMP9 activity by protecting it from degradation 38 . MMP-9, NGAL and some interleukins, have been previously studied as potential biomarkers for UTI, particularly in infants and children, however, conclusions were contradictory 39–44 .…”

Section: Discussionmentioning

confidence: 99%

Identification of clinical and urine biomarkers for uncomplicated urinary tract infection using machine learning algorithms

Gadalla

Friberg

Kift-Morgan

et al. 2019

Sci Rep

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Women with uncomplicated urinary tract infection (UTI) symptoms are commonly treated with empirical antibiotics, resulting in overuse of antibiotics, which promotes antimicrobial resistance. Available diagnostic tools are either not cost-effective or diagnostically sub-optimal. Here, we identified clinical and urinary immunological predictors for UTI diagnosis. We explored 17 clinical and 42 immunological potential predictors for bacterial culture among women with uncomplicated UTI symptoms using random forest or support vector machine coupled with recursive feature elimination. Urine cloudiness was the best performing clinical predictor to rule out (negative likelihood ratio [LR−] = 0.4) and rule in (LR+ = 2.6) UTI. Using a more discriminatory scale to assess cloudiness (turbidity) increased the accuracy of UTI prediction further (LR+ = 4.4). Urinary levels of MMP9, NGAL, CXCL8 and IL-1β together had a higher LR+ (6.1) and similar LR− (0.4), compared to cloudiness. Varying the bacterial count thresholds for urine culture positivity did not alter best clinical predictor selection, but did affect the number of immunological predictors required for reaching an optimal prediction. We conclude that urine cloudiness is particularly helpful in ruling out negative UTI cases. The identified urinary biomarkers could be used to develop a point of care test for UTI but require further validation.

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Section: Discussionmentioning

confidence: 99%

Identification of clinical and urine biomarkers for uncomplicated urinary tract infection using machine learning algorithms

Gadalla

Friberg

Kift-Morgan

et al. 2019

Sci Rep

View full text Add to dashboard Cite

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“… 16 IL-1β was found to upregulate NGAL in human epithelial cells 16 and to possibly comprise a determinant for circulating NGAL in systemic inflammations. 17 A study found IL-10 overexpression by primary macrophages to enhance their pro-resolution activity in complex inflammation-associated pathologies. 18 Likewise, blocking of NGAL production in macrophages reduced IL-10 protective effects in a kidney ischemia/reperfusion injury model, substantiating NGAL-associated pro-proliferative and anti-inflammatory properties.…”

Section: Introductionmentioning

confidence: 99%

Increase in serum and salivary neutrophil gelatinase-associated lipocalin levels with increased periodontal inflammation

et al. 2020

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Increase in serum and salivary neutrophil gelatinase-associated lipocalin levels with increased periodontal inflammation Objective: This study aimed to determine serum and salivary levels of neutrophil gelatinase-associated lipocalin (NGAL) and evaluate NGAL correlation with key anti-interleukin 10 (IL-10) and pro-inflammatory (IL-1β) cytokines in different severities of periodontal diseases. We also calculated the systemic inflammation using the periodontal inflamed surface area (PISA) to evaluate its correlation with NGAL in the study groups. Methodology: Eighty systemically healthy and non-smoking individuals were separated into four groups of 20: clinically healthy (Group 1), gingivitis (Group 2), stage I generalized periodontitis (Group 3, Grade A), and stage III generalized periodontitis (Group 4, Grade A). Sociodemographic characteristics and periodontal parameters were recorded, and PISA was calculated. The serum and salivary levels of interleukin (IL)-1β, IL-10, and NGAL were determined using the enzyme-linked immunosorbent assay (ELISA). Results: We observed a significant increase in serum and salivary NGAL levels from healthy to periodontitis groups (p=0.000). Group 2 presented significantly higher serum and salivary IL-10 levels and salivary IL-1β levels than Group 3 (p=0.000). Serum and salivary parameters (IL-1β, IL-10, and NGAL levels) were strongly positively correlated to periodontal parameters and PISA values (p=0.000). Groups 2 and 3 showed overlapping PISA values. Conclusion: The overlapping PISA values found in Groups 2 and 3 suggest that gingivitis might progress to a systemic inflammatory burden somewhat comparable to stage I periodontitis. This finding is supported by the higher serum and salivary cytokines/mediators levels in the gingivitis group than in stage I periodontitis group. Serum and salivary NGAL levels increased proportionally to disease severity and PISA. NGAL seems to play a role in the pathogenesis of periodontal disease, within the limitation of our study.

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“…Both cell lines were cultured in DMEM-High Glucose (EuroClone) (17.5 mM glucose) with 10% fetal bovine serum (Biochrom AG), l -glutamine (2 mM), penicillin (100 U/ml) and streptomycin (100 μg/ml) at 37 °C in a humidified atmosphere with 5% CO 2 . After reaching a confluence of about 80%, serum was removed for 24 h (starvation) and subsequently treated with TGF-β (10 ng/ml) or IL-1β (10 ng/ml) [41, 42] in the presence or absence of Canakinumab (5 μg/ml).…”

Section: Methodsmentioning

confidence: 99%

In vitro effects of interleukin (IL)-1 beta inhibition on the epithelial-to-mesenchymal transition (EMT) of renal tubular and hepatic stellate cells

et al. 2019

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BackgroundThe epithelial to mesenchymal transition (EMT) is a multi-factorial biological mechanism involved in renal and hepatic fibrosis and the IL-1 beta has been assumed as a mediator of this process although data are not exhaustive. Therefore, the aim of our study was to evaluate the role of this cytokine in the EMT of renal proximal tubular epithelial cells (HK-2) and stellate cells (LX-2) and the protective/anti-fibrotic effect of its inhibition by Canakinumab (a specific human monoclonal antibody targeted against IL-1beta).MethodsBoth cell types were treated with IL-1 beta (10 ng/ml) for 6 and 24 h with and without Canakinumab (5 μg/ml). As control we used TGF-beta (10 ng/ml). Expression of EMT markers (vimentin, alpha-SMA, fibronectin) were evaluated through western blotting and immunofluorescence. Genes expression for matrix metalloproteinases (MMP)-2 was measured by Real-Time PCR and enzymatic activity by zymography. Cellular motility was assessed by scratch assay.ResultsIL-1 beta induced a significant up-regulation of EMT markers in both cell types and increased the MMP-2 protein expression and enzymatic activity, similarly to TGF-beta. Moreover, IL-1 beta induced a higher rate of motility in HK-2. Canakinumab prevented all these modifications in both cell types.ConclusionsOur results clearly demonstrate the role of IL-1 beta in the EMT of renal/stellate cells and it underlines, for the first time, the therapeutic potential of its specific inhibition on the prevention/minimization of organ fibrosis.Electronic supplementary materialThe online version of this article (10.1186/s12967-019-1770-1) contains supplementary material, which is available to authorized users.

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Interleukin-1β as a driver of renal NGAL production

Cited by 16 publications

References 46 publications

Identification of clinical and urine biomarkers for uncomplicated urinary tract infection using machine learning algorithms

Identification of clinical and urine biomarkers for uncomplicated urinary tract infection using machine learning algorithms

Increase in serum and salivary neutrophil gelatinase-associated lipocalin levels with increased periodontal inflammation

In vitro effects of interleukin (IL)-1 beta inhibition on the epithelial-to-mesenchymal transition (EMT) of renal tubular and hepatic stellate cells

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