Structural biology of the IL‐1 superfamily: Key cytokines in the regulation of immune and inflammatory responses

Krumm, Brian E.; Xiang, Yan; Deng, Junpeng

doi:10.1002/pro.2441

Cited by 72 publications

(63 citation statements)

References 77 publications

(203 reference statements)

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“…IL1ra treatment of these patients controls the relapsing inflammation and even limits magnetic resonance imaging-identified white matter changes in the brain associated with the inflammatory conditions 40,41 . Recent solution of the crystal structure reveals the molecular interactions that allow a greater binding affinity of IL1ra than IL1β itself to the IL1 receptor, thereby resulting in an effective competitive blockade 42 . In a neonatal mouse model of in utero lipopolysaccharide exposure and postnatal hyperoxia exposure, IL1ra treatment was associated with less inflammation and improved alveolarization 43 .…”

Section: Discussionmentioning

confidence: 99%

The NLRP3 inflammasome is critically involved in the development of bronchopulmonary dysplasia

et al. 2015

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The pathogenesis of bronchopulmonary dysplasia (BPD), a devastating lung disease in preterm infants, includes inflammation, the mechanisms of which are not fully characterized. Here we report that the activation of the NLRP3 inflammasome is associated with the development of BPD. Hyperoxia-exposed neonatal mice have increased caspase-1 activation, IL1β and inflammation, and decreased alveolarization. Nlrp3−/− mice have no caspase-1 activity, no IL1β, no inflammatory response and undergo normal alveolarization. Treatment of hyperoxia-exposed mice with either IL1 receptor antagonist to block IL1β or glyburide to block the Nlrp3 inflammasome results in decreased inflammation and increased alveolarization. Ventilated preterm baboons show activation of the NLRP3 inflammasome with increased IL1β: IL1ra ratio. The IL1β:IL1ra ratio in tracheal aspirates from preterm infants with respiratory failure is predictive of the development of BPD. We conclude that early activation of the NLRP3 inflammasome is a key mechanism in the development of BPD, and represents a novel therapeutic target for BPD.

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Section: Discussionmentioning

confidence: 99%

The NLRP3 inflammasome is critically involved in the development of bronchopulmonary dysplasia

et al. 2015

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“…Notably, pretreatment with Kineret reversed the increased sIPSC frequency observed in Il1rn KO mice, further supporting the importance of IL-1ra in the regulation of action potential-dependent GABA release. IL-1ra inhibits signaling by binding to the IL-1R1 and preventing the recruitment of IL-1RAcP, which is critical for the initiation of IL-1R1 signaling (Garlanda et al, 2013; Krumm et al, 2014). We hypothesize that deletion of Il1rn induces a tonic activation of IL-1R1 signaling in presynaptic axon terminals, mediating the observed increase in action potential-dependent GABA release.…”

Section: Discussionmentioning

confidence: 99%

“…The proinflammatory activities of cytokines IL-1α and IL-1β are regulated by an endogenous antagonist (IL-1ra), an IL-1 receptor type 1 (IL-1R1), and a decoy receptor (IL-1R2). Specifically, IL-1ra competes with IL-1 for binding sites on IL-1R1 and thus prevents activation of downstream signaling (Garlanda et al, 2013; Krumm et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

Role of the IL-1 receptor antagonist in ethanol-induced regulation of GABAergic transmission in the central amygdala

Bajo

Herman

Varodayan

et al. 2015

Brain, Behavior, and Immunity

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The IL-1 receptor antagonist (IL-1ra), encoded by the Il1rn gene, is an endogenous antagonist of the IL-1 receptor. Studies ofIl1rn knockout (KO) and wild type (WT) mice identified differences in several ethanol-related behaviors, some of which may be mediated by GABAergic transmission in the central nucleus of the amygdala (CeA). In this study we examined phasic (both evoked and spontaneous) and tonic GABAergic transmission in the CeA of Il1rn KO and WT mice and the ethanol sensitivity of these GABAergic synapses. The mean amplitude of baseline evoked GABAA-inhibitory postsynaptic potentials (IPSPs), and the baseline frequency of spontaneous GABAA-inhibitory postsynaptic currents (sIPSCs), but not the frequency of miniature GABAA-IPSCs (mIPSCs), were significantly increased in KO compared to WT mice, indicating enhanced presynaptic action potential-dependent GABA release in the CeA of KO mice. In KO mice, we also found a cell-type specific switch in the ongoing tonic GABAA receptor conductance such that the tonic conductance in low threshold bursting (LTB) neurons is lost and a tonic conductance in late spiking (LS) neurons appears. Notably, the ethanol-induced facilitation of evoked and spontaneous GABA release was lost in most of the CeA neurons from KO compared to WT mice. Ethanol superfusion increased the sIPSC rise and decay times in both KO and WT mice, suggesting ethanol-induced postsynaptic effects. The pretreatment of CeA slices with exogenous IL-1ra (Kineret; 100 ng/ml) returned sIPSC frequency in KO mice to the levels found in WT. Importantly, Kineret also restored ethanol-induced potentiation of the sIPSC frequency in the KO mice. These results show that IL-1ra regulates baseline GABAergic transmission in the CeA and is critical for the ethanol effects at these synapses.

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“…IL-1b contributes to fever, chemotactic activity, and activation of immune cells. TNF-a is involved in an overall stat of catabolism which leads to the shock-like state associated with burn [16]. IL-6 contributes to B-cell maturation, acute phase protein induction, and regulation of T-cell activation and high levels of IL-6 have been associated with increased rates of morbidity and mortality [17,18].…”

Section: Discussionmentioning

confidence: 99%

Hydrogen-rich saline resuscitation alleviates inflammation induced by severe burn with delayed resuscitation

Wang

Pan

YongYang

et al. 2015

Burns

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Structural biology of the IL‐1 superfamily: Key cytokines in the regulation of immune and inflammatory responses

Cited by 72 publications

References 77 publications

The NLRP3 inflammasome is critically involved in the development of bronchopulmonary dysplasia

The NLRP3 inflammasome is critically involved in the development of bronchopulmonary dysplasia

Role of the IL-1 receptor antagonist in ethanol-induced regulation of GABAergic transmission in the central amygdala

Hydrogen-rich saline resuscitation alleviates inflammation induced by severe burn with delayed resuscitation

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