Clinical prevention is of utmost importance for the management of periodontal diseases. Periodontal disease starts with an inflammatory response in the gingival tissue, and results in alveolar bone ...destruction and subsequent tooth loss. This study aimed to confirm the anti-periodontitis effects of MKE. To confirm this, we studied its mechanism of action using qPCR and WB in LPS-treated HGF-1 cells and RANKL-induced osteoclasts. We found that MKE suppressed proinflammatory cytokine protein expression by inhibiting the TLR4/NF-κB pathway in LPS-PG-induced HGF-1 cells and blocking ECM degradation by regulating the expression of TIMPs and MMPs. We also confirmed that TRAP activity and multinucleated cell formation were reduced in RANKL-stimulated osteoclasts after exposure to MKE. These results were confirmed by inhibiting TRAF6/MAPK expression, which led to the suppression of NFATc1, CTSK, TRAP, and MMP expression at the gene and protein levels. Our results confirmed that MKE is a promising candidate for the management of periodontal disease based on its anti-inflammatory effects and inhibition of ECM degradation and osteoclastogenesis.
The scientific community faces an unexpected and urgent challenge related to the SARS-CoV-2 pandemic and is investigating the role of receptors involved in entry of this virus into cells as well as ...pathomechanisms leading to a cytokine "storm," which in many cases ends in severe acute respiratory syndrome, fulminant myocarditis and kidney injury. An important question is if it may also damage hematopoietic stem progenitor cells?
A subgroup of patients with severe COVID-19 suffers from progression to acute respiratory distress syndrome and multiorgan failure. These patients present with progressive hyperinflammation governed ...by proinflammatory cytokines. An interdisciplinary COVID-19 work flow was established to detect patients with imminent or full blown hyperinflammation. Using a newly developed COVID-19 Inflammation Score (CIS), patients were prospectively stratified for targeted inhibition of cytokine signalling by the Janus Kinase 1/2 inhibitor ruxolitinib (Rux). Patients were treated with efficacy/toxicity guided step up dosing up to 14 days. Retrospective analysis of CIS reduction and clinical outcome was performed. Out of 105 patients treated between March 30th and April 15th
2020, 14 patients with a CIS ≥ 10 out of 16 points received Rux over a median of 9 days with a median cumulative dose of 135 mg. A total of 12/14 patients achieved significant reduction of CIS by ≥25% on day 7 with sustained clinical improvement in 11/14 patients without short term red flag warnings of Rux-induced toxicity. Rux treatment for COVID-19 in patients with hyperinflammation is shown to be safe with signals of efficacy in this pilot case series for CRS-intervention to prevent or overcome multiorgan failure. A multicenter phase-II clinical trial has been initiated (NCT04338958).
Forty years after its naming, interleukin-1 (IL-1) is experiencing a renaissance brought on by the growing understanding of its context-dependent roles and advances in the clinic. Recent studies have ...identified important roles for members of the IL-1 family—IL-18, IL-33, IL-36, IL-37, and IL-38—in inflammation and immunity. Here, we review the complex functions of IL-1 family members in the orchestration of innate and adaptive immune responses and their diversity and plasticity. We discuss the varied roles of IL-1 family members in immune homeostasis and their contribution to pathologies, including autoimmunity and auto-inflammation, dysmetabolism, cardiovascular disorders, and cancer. The trans-disease therapeutic activity of anti-IL-1 strategies argues for immunity and inflammation as a metanarrative of modern medicine.
Mantovani et al. review the complex functions of IL-1 family members in the orchestration of innate and adaptive immune responses and discuss how our growing understanding of the context-dependent roles of these cytokines are informing advances in the clinic.
Macrophages activated by type 2 cytokines can produce IGF‐1 that switches the eating preferences of neighboring epithelial cells, reducing their phagocytosis of apoptotic cells and enhancing their ...uptake of macrophage‐secreted microvesicles, the latter resulting in reduced production of inflammatory cytokines by epithelial cells.
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