Author Correction: Inflammasome components as new therapeutic targets in inflammatory disease
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Caspase-11 mediated inflammasome activation in macrophages by systemic infection of A. actinomycetemcomitans exacerbates arthritis
Clinical studies have shown that Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) is associated with aggressive periodontitis and can potentially trigger or exacerbate rheumatoid arthritis (RA). However, the mechanism is poorly understood. Here, we show that systemic infection with A. actinomycetemcomitans triggers the progression of arthritis in mice anti-collagen antibody-induced arthritis (CAIA) model following IL-1β secretion and cell infiltration in paws in a manner that is dependent on caspase-11-mediated inflammasome activation in macrophages. The administration of polymyxin B (PMB), chloroquine, and anti-CD11b antibody suppressed inflammasome activation in macrophages and arthritis in mice, suggesting that the recognition of lipopolysaccharide (LPS) in the cytosol after bacterial degradation by lysosomes and invasion via CD11b are needed to trigger arthritis following inflammasome activation in macrophages. These data reveal that the inhibition of caspase-11-mediated inflammasome activation potentiates aggravation of RA induced by infection with A. actinomycetemcomitans. This work highlights how RA can be progressed by inflammasome activation as a result of periodontitis-associated bacterial infection and discusses the mechanism of inflammasome activation in response to infection with A. actinomycetemcomitans.
Role of macrophage in intervertebral disc degeneration
Intervertebral disc degeneration is a degenerative disease where inflammation and immune responses play significant roles. Macrophages, as key immune cells, critically regulate inflammation through polarization into different phenotypes. In recent years, the role of macrophages in inflammation-related degenerative diseases, such as intervertebral disc degeneration, has been increasingly recognized. Macrophages construct the inflammatory microenvironment of the intervertebral disc and are involved in regulating intervertebral disc cell activities, extracellular matrix metabolism, intervertebral disc vascularization, and innervation, profoundly influencing the progression of disc degeneration. To gain a deeper understanding of the inflammatory microenvironment of intervertebral disc degeneration, this review will summarize the role of macrophages in the pathological process of intervertebral disc degeneration, analyze the regulatory mechanisms involving macrophages, and review therapeutic strategies targeting macrophage modulation for the treatment of intervertebral disc degeneration. These insights will be valuable for the treatment and research directions of intervertebral disc degeneration.
The ability of microRNAs to regulate the immune response in ischemia/reperfusion inflammatory pathways
MicroRNAs play a crucial role in regulating the immune responses induced by ischemia/reperfusion injury. Through their ability to modulate gene expression, microRNAs adjust immune responses by targeting specific genes and signaling pathways. This review focuses on the impact of microRNAs on the inflammatory pathways triggered during ischemia/reperfusion injury and highlights their ability to modulate inflammation, playing a critical role in the pathophysiology of ischemia/reperfusion injury. Dysregulated expression of microRNAs contributes to the pathogenesis of ischemia/reperfusion injury, therefore targeting specific microRNAs offers an opportunity to restore immune homeostasis and improve patient outcomes. Understanding the complex network of immunoregulatory microRNAs could provide novel therapeutic interventions aimed at attenuating excessive inflammation and preserving tissue integrity.
IL-1β drives SARS-CoV-2-induced disease independently of the inflammasome and pyroptosis signalling
Excessive inflammation and cytokine release are hallmarks of severe COVID-19. Certain programmed cell death processes can drive inflammation, however, their role in the pathogenesis of severe COVID-19 is unclear. Pyroptosis is a pro-inflammatory form of regulated cell death initiated by inflammasomes and executed by the pore-forming protein gasdermin D (GSDMD). Using an established mouse adapted SARS-CoV-2 virus and a panel of gene-targeted mice we found that deletion of the inflammasome (NLRP1/3 and the adaptor ASC) and pore forming proteins involved in pyroptosis (GSDMA/C/D/E) only marginally reduced IL-1β levels and did not impact disease outcome or viral loads. Furthermore, we found that SARS-CoV-2 infection did not trigger GSDMD activation in mouse lungs. Finally, we did not observe any difference between WT animals and mice with compound deficiencies in the pro-inflammatory initiator caspases (C1/11/12−/−). This indicates that the classical canonical and non-canonical pro-inflammatory caspases known to process and activate pro-IL-1β, pro-IL-18 and GSDMD do not substantially contribute to SARS-CoV-2 pathogenesis. However, the loss of IL-1β, but not the absence of IL-18, ameliorated disease and enhanced survival in SARS-CoV-2 infected animals compared to wildtype mice. Collectively, these findings demonstrate that IL-1β is an important factor contributing to severe SARS-CoV-2 disease, but its release was largely independent of inflammasome and pyroptotic pathways.
Cross-talk of inflammation and cellular senescence: a new insight into the occurrence and progression of osteoarthritis
Osteoarthritis (OA) poses a significant challenge in orthopedics. Inflammatory pathways are regarded as central mechanisms in the onset and progression of OA. Growing evidence suggests that senescence acts as a mediator in inflammation-induced OA. Given the lack of effective treatments for OA, there is an urgent need for a clearer understanding of its pathogenesis. In this review, we systematically summarize the cross-talk between cellular senescence and inflammation in OA. We begin by focusing on the mechanisms and hallmarks of cellular senescence, summarizing evidence that supports the relationship between cellular senescence and inflammation. We then discuss the mechanisms of interaction between cellular senescence and inflammation, including senescence-associated secretory phenotypes (SASP) and the effects of pro- and anti-inflammatory interventions on cellular senescence. Additionally, we focus on various types of cellular senescence in OA, including senescence in cartilage, subchondral bone, synovium, infrapatellar fat pad, stem cells, and immune cells, elucidating their mechanisms and impacts on OA. Finally, we highlight the potential of therapies targeting senescent cells in OA as a strategy for promoting cartilage regeneration.
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