The alarmin IL-1α is a master cytokine in acute lung inflammation induced by silica micro- and nanoparticles

Abstract

BackgroundInflammasome-activated IL-1β plays a major role in lung neutrophilic inflammation induced by inhaled silica. However, the exact mechanisms that contribute to the initial production of precursor IL-1β (pro-IL-1β) are still unclear. Here, we assessed the implication of alarmins (IL-1α, IL-33 and HMGB1) in the lung response to silica particles and found that IL-1α is a master cytokine that regulates IL-1β expression.MethodsPro- and mature IL-1β as well as alarmins were assessed by ELISA, Western Blot or qRT-PCR in macrophage cultures and in mouse lung following nano- and micrometric silica exposure. Implication of these immune mediators in the establishment of lung inflammatory responses to silica was investigated in knock-out mice or after antibody blockade by evaluating pulmonary neutrophil counts, CXCR2 expression and degree of histological injury.ResultsWe found that the early release of IL-1α and IL-33, but not HMGB1 in alveolar space preceded the lung expression of pro-IL-1β and neutrophilic inflammation in silica-treated mice. In vitro, the production of pro-IL-1β by alveolar macrophages was significantly induced by recombinant IL-1α but not by IL-33. Neutralization or deletion of IL-1α reduced IL-1β production and neutrophil accumulation after silica in mice. Finally, IL-1α released by J774 macrophages after in vitro exposure to a range of micro- and nanoparticles of silica was correlated with the degree of lung inflammation induced in vivo by these particles.ConclusionsWe demonstrated that in response to silica exposure, IL-1α is rapidly released from pre-existing stocks in alveolar macrophages and promotes subsequent lung inflammation through the stimulation of IL-1β production. Moreover, we demonstrated that in vitro IL-1α release from macrophages can be used to predict the acute inflammogenic activity of silica micro- and nanoparticles.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-014-0069-x) contains supplementary material, which is available to authorized users.

No involvement of alveolar macrophages in the initiation of carbon nanoparticle induced acute lung inflammation in mice

“…Due to contaminations in ambient PM samples, such as airborne bacterial endotoxin or reactive metallic compounds, the described PM triggered induction of the pro-inflammatory cytokine release for AMs may however differ from that driven by pure carbon particles. On a related note, the initiation of CNP triggered inflammation seems also independent from the alarmin release mechanism, recently uncovered for crystalline silica particles [39]. In their study the authors describe the release of the tissue damage alarmin IL-1α from AM directly after pulmonary silica particle deposition.…”

“…Particle phagocytosis of needle like shapes or particular crystals can combined with the material specific high surface reactivity cause lysosomal destabilization, which sensed by the NALP3 inflammasome, leads to the release of the proinflammatory master cytokine IL-1β from particle laden macrophages [37,38]. In addition to that, IL-α had been described as a alarmin cytokine, upstream of IL-1β, which is released from AM already in the first hours after silica particle deposition [39]. None of these activation mechanisms have so far been observed for pyrogenfree, spherical carbon nanoparticles, and a specific role of AM in sensing these particles as a danger pattern remains uncertain.…”

Particles from the Echinococcus granulosus laminated layer inhibit IL-4 and growth factor-driven Akt phosphorylation and proliferative responses in macrophages

“…Particulate inflammatory stimuli generally cause disappearance of resident macrophages and recruitment of macrophages of bone marrow origin464748495051, two phenomena that we will refer to together as “disappearance-recruitment”. pLL, especially at high doses, causes “disappearance-recruitment” (Figs 1B, 2B and S3A,B; data not shown), indicative of potential to elicit acute inflammation.…”

Interleukin 1 gene polymorphism and susceptibility to disease

“…Such a response is observed, for example, in response to sterile injury or infection . Upon cell necrosis, the release of IL‐1α to the extracellular environment and its binding to the respective IL‐1R receptor on target cells, promotes cell activation and pro‐inflammatory gene transcription via the nuclear factor‐κB (NFκB) pathway …”