A5073734104- Cancer, Stress, Anesthesia, and Immune Response
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Neuroinflammation and Neurodegeneration Mechanisms
- Phagocytosis and Immune Regulation
- Inflammasome and immune disorders
- interferon and immune responses
- IL-33, ST2, and ILC Pathways
- Spinal Cord Injury Research
- Immune Cell Function and Interaction
- Cancer Research and Treatments
- Chemokine receptors and signaling
- Eicosanoids and Hypertension Pharmacology
- Cytokine Signaling Pathways and Interactions
- Neuroblastoma Research and Treatments
- Pancreatic and Hepatic Oncology Research
- Histone Deacetylase Inhibitors Research
- Immune Response and Inflammation
- Cancer Cells and Metastasis
- PARP inhibition in cancer therapy
- Autoimmune and Inflammatory Disorders Research
- Tryptophan and brain disorders
- Cancer Genomics and Diagnostics
- Immunotherapy and Immune Responses
- Cancer, Lipids, and Metabolism
University of Colorado Anschutz Medical Campus
2023-2024
University of Colorado Denver
2020-2024
Universitat Autònoma de Barcelona
2016-2022
Centro de Investigación Biomédica en Red
2018-2022
Biomedical Research Networking Center on Neurodegenerative Diseases
2016-2022
Macrophages and microglia play a key role in the maintenance of nervous system homeostasis. However, upon different challenges, they can adopt several phenotypes, which may lead to divergent effects on tissue repair. After spinal cord injury (SCI), macrophages show predominantly pro-inflammatory activation contribute damage. factors that hamper their conversion an anti-inflammatory state after SCI, or other protective are poorly understood. Here, we IL-4 protein levels undetectable contusion...
Abstract Background Parkinson’s disease (PD) is characterized by a progressive degeneration of dopaminergic neurons, which leads to irreversible loss peripheral motor functions. Death neurons induces an inflammatory response in microglial cells, further exacerbates neuronal loss. Reducing inflammation expected ameliorate and arrest dysfunctions. Because the contribution NLRP3 inflammasome PD, we targeted using specific inhibitor OLT1177 ® . Methods We evaluated effectiveness reducing MPTP...
Spinal cord injury (SCI) usually causes a devastating lifelong disability for patients. After traumatic lesion, disruption of the blood-spinal barrier induces infiltration macrophages into lesion site and activation resident glial cells, which release cytokines chemokines. These events result in persistent inflammation, has both detrimental beneficial effects, but eventually limits functional recovery contributes to appearance neuropathic pain. Bromodomain extra-terminal domain (BET)...
The IL-1 family member IL-37 broadly suppresses innate inflammation and acquired immunity. Similar to IL-1α IL-33, is a dual-function cytokine in that translocates the nucleus but also transmits signal via surface membrane receptors. role of nuclear remains unknown on ability this inhibit inflammation. Here, we compared suppression transgenic mice expressing native human (IL-37Tg) with those carrying mutation aspartic acid (D) alanine (A) at amino 20 (IL-37D20ATg). D20A prevents cleavage...
Background: Microglia and macrophages adopt a pro-inflammatory phenotype after spinal cord injury (SCI), what is thought to contribute secondary tissue degeneration.We previously reported that this due, in part, the low levels of anti-inflammatory cytokines, such as IL-4.Since IL-13 IL-4 share receptors both cytokines drive microglia towards an vitro, here we studied whether administration SCI leads beneficial effects.Methods: We injected mice with recombinant or at 48 h assessed their...
A role for microglia in neuropsychiatric diseases, including major depressive disorder (MDD), has been postulated. Regulation of microglial phenotype by immune receptors become a central topic many neurological conditions. We explored preclinical and clinical evidence the CD300f receptor fine regulation its contribution to MDD. found that prevalent nonsynonymous single-nucleotide polymorphism (C/T, rs2034310) human cytoplasmic tail inhibits protein kinase C phosphorylation threonine is...
Background: Interleukin 37 (IL-37), a member of IL-1 family, broadly suppresses inflammation in many pathological conditions by acting as dual-function cytokine that IL-37 signals via the extracellular receptor complex IL1-R5/IL-1R8, but it can also translocate to nucleus. However, whether exerts beneficial actions neuroinflammatory diseases, such multiple sclerosis, remains be elucidated. Thus, goals present study were evaluate therapeutic effects mouse model and if so, this is mediated...
IL-38 is a recently discovered cytokine and member of the IL-1 Family. In Family, unique because primarily B lymphocyte product functions to suppress inflammation. Studies in humans with inflammatory bowel disease (IBD) suggest that may be protective for ulcerative colitis or Crohn’s disease, acts maintain homeostasis intestinal tract. Here we investigated role endogenous experimental mice deficient by deletion exons 1-4 C57 BL/6 mice. Compared WT mice, subjected dextran sulfate sodium (DSS)...
Defining feature of pancreatic ductal adenocarcinoma (PDAC) that participates in the high mortality rate and drug resistance is immune-tolerant microenvironment which enables tumors to progress unabated by adaptive immunity. In this study, we report PDAC cells release CSF-1 induce nucleotide-binding domain, leucine-rich containing family, pyrin domain-containing-3 (NLRP3) activation myeloid cells. Increased NLRP3 expression was found pancreas patients with when compared normal correlated...
Abstract Spinal cord injury (SCI) leads to irreversible devastating neurological disabilities. Accumulated evidence in the literature indicates that inflammatory response occurs spinal following contributes importantly spread tissue damage healthy regions adjacent lesion site, and consequently, increase deficits. Therefore, targeting inflammation could lead development of new therapies prevent impairments after SCI. Inflammation is regulated, part, by expression pro‐inflammatory...
Introduction Interleukin-18 (IL-18), a pro-inflammatory cytokine belonging to the IL-1 Family, is key mediator ofautoinflammatory diseases associated with development of macrophage activation syndrome (MAS).High levels IL-18 correlate MAS and COVID-19 severity mortality, particularly in COVID-19patients MAS. As an inflammation inducer, binds its receptor Receptor 5 (IL-1R5), leadingto recruitment co-receptor, 7 (IL-1R7). This heterotrimeric complex subsequentlyinitiates downstream signaling,...
The IL-1 Family member IL-38 has been characterized primarily as an antiinflammatory cytokine in human and mouse models of systemic diseases. Here, we examined the role murine small intestine (SI). Immunostaining SI revealed that expression partially confines to intestinal stem cells. Cultures organoids reveal functions a growth factor by increasing organoid size via inducing WNT3a. In contrast, from IL-38-deficient mice develop more slowly. This reduction is likely due downregulation...
Metabolism is a fundamental process by which biochemicals are broken down to produce energy (catabolism) or used build macromolecules (anabolism). has received renewed attention as mechanism that generates molecules modulate multiple cellular responses. This was first identified in cancer cells the Warburg effect, but it also present immunocompetent cells. Studies have revealed bidirectional influence of metabolism and immune cell function, highlighting significance metabolic reprogramming...
Activating and inhibitory immune receptors play a critical role in regulating systemic central nervous system (CNS) inflammatory processes. The CD200R1 immunoreceptor induces restraining signal modulating inflammation phagocytosis the CNS under different conditions. However, it remains unknown whether has response after peripheral nerve injury, an essential component of successful regeneration. Expression its ligand CD200 was analyzed during homeostasis sciatic crush injury C57Bl/6 mice....
Abstract The IL-1 Family member IL-38 has been characterized primarily as an anti-inflammatory cytokine in human and mouse models of systemic diseases. Here, we examined the role murine small intestine (SI). Immunostaining SI revealed that expression partially confines to intestinal stem cells. Cultures organoids reveal functions a growth factor by increasing organoid size via inducing WNT3a. In contrast, from deficient mice develop more slowly. This reduction is likely due downregulation...
<p>PDAC paracrine activity mediates NLRP3 activation. <b>A,</b> IL1β and IL18 secretion from freshly isolated PBMCs healthy donors (<i>n</i> = 6) following stimulation with PDAC-conditioned media obtained AsPC-1, MiaPaCa-2, Panc-1 cells. <b>B,</b> parenteral (WT) deficient (NLRP3<sup>−/−</sup>) THP-1 cells 3). <b>C,</b> in presence of the inhibitors OLT1177 (OLT) MCC950 (MCC; <i>n</i> Cytokine levels were measured...
<p>CSF-1R engagement induces IL1β and IL18 release. <b>A,</b> Correlation between CSF-1R NLRP3 expression in PDAC (<i>n</i> = 96) from TGCA dataset. <b>B,</b> Spontaneous CSF-1 IL34 secretion Panc-1 cells at 72 hours 3). <b>C,</b> THP-1 following stimulation with PDAC-conditioned media obtained presence of IgG (control), α-CSF-1, α-IL34, α-CSF-1/IL34 <b>D,</b> Phosphorylation levels PyK2 (Tyrosine 402) stimulated D E...
<p>NLRP3 activation mediates a Th2-like inflammatory response. <b>A,</b> Flow cytometry analysis of CD4, CD4/PD1, CD4/CD44/PD-1 cells in primary tumors mice fed standard (STD) and OLT1177 (OLT)-enriched diets (<i>n</i> = 5/group). <b>B,</b> memory (CD62L<sup>+</sup>/CD44<sup>+</sup>), naïve (CD62L<sup>+</sup>/CD44<sup>−</sup>), effector (CD62L<sup>−</sup>/CD44<sup>+</sup>) CD4...
<p>Level of NLRP3, IL 1b and 18 in PDAC cells.</p>
<p>OLT1177 levels in mice.</p>
<div><p>Defining feature of pancreatic ductal adenocarcinoma (PDAC) that participates in the high mortality rate and drug resistance is immune-tolerant microenvironment which enables tumors to progress unabated by adaptive immunity. In this study, we report PDAC cells release CSF-1 induce nucleotide-binding domain, leucine-rich containing family, pyrin domain-containing-3 (NLRP3) activation myeloid cells. Increased NLRP3 expression was found pancreas patients with when compared...