IL-1 receptor 2 (IL-1R2) and its role in immune regulation

Peters, Vera; Joesting, Jennifer J.; Freund, Gregory G.

doi:10.1016/j.bbi.2012.11.006

Cited by 193 publications

(165 citation statements)

References 97 publications

(106 reference statements)

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“…For example, IL1R2 was found to be positively correlated with reduced insulin secretion and higher HbA1c levels[38]; VPS4B was up-regulated in response to the inhibition of glucose stimulated insulin secretion[39]; and CAP1 expression level was associated with insulin sensitivity[40]. These studies corroborate our findings and strengthen the premise that our panel could be used in the clinical detection of IR.…”

Section: Discussionsupporting

confidence: 79%

Salivary extracellular RNA biomarkers for insulin resistance detection in hispanics

Zhang

Sun

et al. 2017

Diabetes Research and Clinical Practice

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Aims Insulin resistance (IR) detection is challenging and no test is currently used in clinical practice. We developed salivary biomarkers that could be used for IR detection. Methods We collected saliva from 186 healthy and 276 pre-diabetic participants, divided them into high and low IR groups based on a HOMA cutoff of 2.5. We profiled extracellular transcriptome by microarray in saliva supernatant from 23 high IR and 15 low IR participants, and pre-validated the top ten extracellular mRNA (exRNA) markers in a new cohort of 40 high and 40 low IR participants. A prediction panel was then built and validated in an independent cohort of 149 high and 195 low IR participants. Results Transcriptomic analyses identified 42 exRNA candidates differentially present in saliva of high and low IR participants. From the top ten candidates, six were individually validated (PRKCB, S100A12, IL1R2, CAMP, VPS4B, CAP1) (p<0.01) and yielded AUC values ranging from 0.66 to 0.76. Body mass index (BMI) was significant higher in high compared to low IR group with AUC of 0.66, and showed no correlation with any of candidate biomarkers. The combination of four exRNA markers (IL1R2, VPS4B, CAP1, LUZP6) with BMI achieved excellent results in the prediction panel building dataset (AUC=0.79, sensitivity=79%, specificity=64%). The prediction model was validated in an independent cohort (AUC=0.82, sensitivity=63%, specificity=92%). Conclusions A panel of four salivary exRNA biomarkers (IL1R2, VPS4B, CAP1, LUZP6) and BMI was validated that can distinguish high and low IR participants, overall and in subgroups of healthy and pre-diabetic participants.

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Section: Discussionsupporting

confidence: 79%

Salivary extracellular RNA biomarkers for insulin resistance detection in hispanics

Zhang

Sun

et al. 2017

Diabetes Research and Clinical Practice

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“…Unlike IL-1RA, which exists in a single form, IL-1R2 exists in two forms one which is membrane bound and one which is soluble (sIL-1R2) (43). As with IL-1RA, IL-1R2 serves as a negative regulator of IL-1 signaling, but instead of blocking the IL-1R1 receptor as does IL-1RA, IL-1R2 competes with the IL-1R1 for IL-1.…”

Section: Discussionmentioning

confidence: 99%

Fasting Induces IL-1 Resistance and Free-Fatty Acid-Mediated Up-Regulation of IL-1R2 and IL-1RA

et al. 2014

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Objective: Weight-loss is a near societal obsession and many diet programs use significant calorie restriction including fasting/short term starvation to generate rapid effects. Fasting is also a well-recognized cause of immunosuppression especially within the innate immune system. In this study, we sought to determine if the IL-1 arm of the neuroimmune system was down-regulated by a 24 h fast and how fasting might generate this effect.Design: Mice were allowed ad libitum access to food or had food withheld for 24 h. Expression of the endogenous IL-1 antagonists, IL-1 receptor type 2 (IL-1R2), and IL-1 receptor antagonist (IL-1RA) was determined as were sickness behaviors before and after IL-1β administration.Results: Fasting markedly increased gene expression of IL-1R2 (83-fold in adipose tissue, 9.5-fold in liver) and IL-1RA (68-fold in liver). Fasted mice were protected from IL-1β-induced weight-loss, hypoglycemia, loss of locomotor, and social anxiety. These protections were coupled to a large positive interaction of fasting and IL-1β on IL-1R2 gene expression in adipose tissue and liver (2.6- and 1.6-fold, respectively). Fasting not only increased IL-1RA and IL-1R2 protein 2.5- and 3.2-fold, respectively, in liver but also increased IL-1R2 1.8-fold in adipose tissue. Fasting, in turn, triggered a 2.4-fold increase in plasma free-fatty acids (FFAs) and a 2.1-fold increase in plasma corticosterone. Inhibition, of glucocorticoid action with mifepristone did not impact fasting-dependent IL-1R2 or IL-1RA gene expression. Administration of the FFA, palmitate, to mice increased liver IL-1R2 and IL-1RA gene expression by 14- and 11-fold, respectively.Conclusion: These findings indicate that fasting augments expression of endogenous IL-1 antagonists inducing IL-1 resistance. Fasting-induced increases in plasma FFAs appears to be a signal that drives immunosuppression during fasting/short term starvation.

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“…Intrathecal inflammation in these children is counterbalanced by the increased production of interleukin 1 receptor antagonist (IL-1Ra), a natural endogenous antagonist of IL-1, critical for a variety of brain effects (Arend, 2002; Gadek-Michalska and Bugajski, 2010; Akash et al, 2013; Peters et al, 2013). IL-1RA exhibits low uptake in the normal brain, with rapid metabolism, a short biological half-life (4–6 h), and excretion via the kidneys (Cawthorne et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Brain immune interactions and air pollution: macrophage inhibitory factor (MIF), prion cellular protein (PrPC), Interleukin-6 (IL-6), interleukin 1 receptor antagonist (IL-1Ra), and interleukin-2 (IL-2) in cerebrospinal fluid and MIF in serum differentiate urban children exposed to severe vs. low air pollution

Calderón‐Garcidueñas¹,

Cross²,

Franco-Lira³

et al. 2013

Front. Neurosci.

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Mexico City Metropolitan Area children chronically exposed to high concentrations of air pollutants exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, innate and adaptive immune responses along with accumulation of misfolded proteins observed in the early stages of Alzheimer and Parkinson's diseases. A complex modulation of serum cytokines and chemokines influences children's brain structural and gray/white matter volumetric responses to air pollution. The search for biomarkers associating systemic and CNS inflammation to brain growth and cognitive deficits in the short term and neurodegeneration in the long-term is our principal aim. We explored and compared a profile of cytokines, chemokines (Multiplexing LASER Bead Technology) and Cellular prion protein (PrPC) in normal cerebro-spinal-fluid (CSF) of urban children with high vs. low air pollution exposures. PrPC and macrophage inhibitory factor (MIF) were also measured in serum. Samples from 139 children ages 11.91 ± 4.2 years were measured. Highly exposed children exhibited significant increases in CSF MIF (p = 0.002), IL6 (p = 0.006), IL1ra (p = 0.014), IL-2 (p = 0.04), and PrPC (p = 0.039) vs. controls. MIF serum concentrations were higher in exposed children (p = 0.009). Our results suggest CSF as a MIF, IL6, IL1Ra, IL-2, and PrPC compartment that can possibly differentiate air pollution exposures in children. MIF, a key neuro-immune mediator, is a potential biomarker bridge to identify children with CNS inflammation. Fine tuning of immune-to-brain communication is crucial to neural networks appropriate functioning, thus the short and long term effects of systemic inflammation and dysregulated neural immune responses are of deep concern for millions of exposed children. Defining the linkage and the health consequences of the brain / immune system interactions in the developing brain chronically exposed to air pollutants ought to be of pressing importance for public health.

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IL-1 receptor 2 (IL-1R2) and its role in immune regulation

Cited by 193 publications

References 97 publications

Salivary extracellular RNA biomarkers for insulin resistance detection in hispanics

Salivary extracellular RNA biomarkers for insulin resistance detection in hispanics

Fasting Induces IL-1 Resistance and Free-Fatty Acid-Mediated Up-Regulation of IL-1R2 and IL-1RA

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