A5071956291- Inflammasome and immune disorders
- Immune cells in cancer
- Immune Response and Inflammation
- Cancer Immunotherapy and Biomarkers
- Gout, Hyperuricemia, Uric Acid
- Cytokine Signaling Pathways and Interactions
- Autoimmune and Inflammatory Disorders Research
- Dermatology and Skin Diseases
- Autophagy in Disease and Therapy
- Erythrocyte Function and Pathophysiology
- Exercise and Physiological Responses
- Colorectal Cancer Screening and Detection
- Urinary and Genital Oncology Studies
- SARS-CoV-2 and COVID-19 Research
- Diet, Metabolism, and Disease
- Bladder and Urothelial Cancer Treatments
- Kawasaki Disease and Coronary Complications
- Immunotherapy and Immune Responses
- IL-33, ST2, and ILC Pathways
University of Colorado Anschutz Medical Campus
2019-2023
University of Colorado Denver
2018-2023
Thomas Jefferson University
2022
Western University
2020
University of Cambridge
1967
Significance The nucleotide-binding domain, leucine-rich containing family, pyrin domain-containing-3 (NLRP3) inflammasome, an intracellular complex that regulates maturation and release of interleukin (IL)-1β, is active in biopsies metastatic melanoma. Here, we demonstrate NLRP3 activation melanoma cells drives tumor progression mice. Subsequent to cells, IL-1β induces melanoma-associated inflammation, resulting immunosuppression. Oral administration a single inhibitor (OLT1177) reduces...
Activation of the NLRP3 inflammasome in gout amplifies inflammatory response and mediates further damage. In current study, we assessed therapeutic effect OLT1177, an orally active inhibitor that is safe humans, murine acute arthritis models. Zymosan or monosodium urate (MSU) crystals were injected intra-articularly (i.a.) into mouse knee joints to induce reactive gouty arthritis. Joint swelling, articular cell infiltration, synovial cytokines evaluated 25 hours 4 following zymosan MSU...
Tumors evade the immune system by inducing inflammation. In melanoma, tumor-derived IL-1β drives inflammation and expansion of highly immunosuppressive myeloid-derived suppressor cells (MDSCs). Similar in many tumors, melanoma is also linked to downstream IL‐6/STAT3 axis. this study, we observed that both recombinant specifically induce pSTAT3(Y705), creating a tumor-autoinflammatory loop, which amplifies IL-6 signaling human cell line 1205Lu. To disrupt IL-1β/IL-6/STAT3 axis, suppressed...
Nucleoside modified mRNA combined with Acuitas Therapeutics’ lipid nanoparticles (LNPs) has been shown to support robust humoral immune responses in many preclinical animal vaccine studies and later humans the SARS-CoV-2 vaccination. We recently showed that this platform is highly inflammatory due LNPs’ ionizable component. The property key development of potent responses. However, mechanism by which drives T follicular helper (Tfh) cells remains unknown. Here we show lack Langerhans or...
Interleukin-1 (IL-1) is a key mediator of inflammation and immunity. Naturally-occurring IL-1 receptor antagonist (IL-1Ra) binds blocks the receptor-1 (IL-1R1), preventing signaling. Anakinra, recombinant form IL-1Ra, used to treat spectrum inflammatory diseases. However, anakinra rapidly cleared from body requires daily administration. To create longer-lasting alternative, PASylated IL-1Ra (PAS–IL-1Ra) has been generated by in-frame fusion long, defined-length, N-terminal Pro/Ala/Ser (PAS)...
Tumor-associated inflammation leads to dysregulated cytokine production that promotes tumor immune evasion and anti-tumor immunity dysfunction. In advanced stage breast cancer, the proinflammatory IL-1β is overexpressed due large proportions of activated myeloid cells in microenvironment (TME). Here, we demonstrate role host nucleotide-binding domain, leucine-rich containing family, pyrin domain-containing 3 (NLRP3) inflammasome metastatic cancer. vitro, show stimulation THP-1 with...
Unchecked inflammation can result in severe diseases with high mortality, such as macrophage activation syndrome (MAS). MAS and associated cytokine storms have been observed COVID-19 patients exhibiting systemic hyperinflammation. Interleukin-18 (IL-18), a proinflammatory belonging to the IL-1 family, is elevated both patients, its level known correlate severity of symptoms. IL-18 binds specific receptor 5 (IL-1R5, also alpha chain), leading recruitment coreceptor, 7 (IL-1R7, beta chain)....
Reticuloendothelial macrophages engulf ~0.2 trillion senescent erythrocytes daily in a process called erythrophagocytosis (EP). This critical mechanism preserves systemic heme-iron homeostasis by regulating red blood cell (RBC) catabolism and iron recycling. Although extensive work has demonstrated the various effects on macrophage metabolic reprogramming stimulation with proinflammatory cytokines, little is known about impact of EP metabolome proteome. Thus, we performed mass...
The NLRP3 inflammasome is a multimolecular complex that processes inactive IL-1β and IL-18 into proinflammatory cytokines. OLT1177 an orally active small compound specifically inhibits NLRP3. Here, B16F10 melanoma were implanted in mice treated with as well combined the glucocorticoid dexamethasone. At sacrifice, had significantly smaller tumors compared to tumor-bearing vehicle. However, treatment of plus dexamethasone revealed greater suppression tumor growth. This reduction was...
Bladder Cancer Canada (BCC), Canadian Urologic Oncology Group (CUOG), and Urological Association (CUA)". 1 This was a summary report of the committee's consensus deliberations during first twoday BCC-CUA-CUOG Quality Care Meeting (BCQCM) held in late 2014.One recommendations from to perform Delphi process establish set quality indicators across important categories bladder cancer care. undertaken, led 2017 publication listing 60 for consideration. 2 In November 2016, another...