Browsing by Subject "immune cells"

Now showing 1 - 4 of 4
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    Chlorpyrifos Oxon Primes Microglia: Enhanced LPS-Induced TNFα Production
    (Office of the Vice Chancellor for Research, 2016-04-08) Kouame, Elaine; Brookins, Savannah; Jayaraj, Richard L.; Taetzsch, Thomas; Mumaw, Christy; Block, Michelle L.
    Microglia, the resident innate immune cells of the brain, respond to various environmental stimuli, including factors from surrounding tissue and from systemic inputs. These stimuli impact microglial function in both health and disease. Increasing evidence implicates microglia and neuroinflammation in Gulf War illness (GWI) pathology. Gulf War illness is an untreatable chronic multi symptomatic disorder that affects about 30% of Gulf War veterans. It has been proposed that “multiple hits” from exposure to various environmental neurotoxicants such as Chlorpyrifos (CPF), an organophosphate pesticide, combined with low inflammation may initiate exaggerated and persistent central nervous system (CNS) pathology to drive GWI. CPF oxon, an active metabolite of CPF, is associated with deleterious CNS effects, but the role of microglia behind this phenomenon is not fully understood.To investigate the effects of CPF oxon on microglia, we assessed microglial ROS, pro-inflammatory cytokine factors, and NF-κB p50 DNA binding activity in the presence of CPF oxon. HAPI microglia cells were treated with CPF oxon (1μM-1nM), which resulted in a dose dependent increase in H2O2 production at 3 hours and elevated superoxide at 30 minutes. CPF oxon failed to initiate TNFα and nitric oxide from microglia cultures. However, CPF oxon significantly decreased NF-κB p50 binding to DNA in microglia, a key redox signaling mechanism linked to microglial priming. Consistent with this premise, pre-treatment with CPF oxon (0.5μM) amplified LPSinduced TNFα production in microglia and neuron-glia cultures. Moreover, when CPF oxon and LPS challenged cells were pre-treated with DPI, a NOX2 inhibitor, we found a significant reduction in TNFα response when compared to non-treated cells, supporting that NOX2 may regulate CPF oxon priming in microglia. These data suggest that CPF oxon may induce ROS production in microglia to reprogram these cells to become more sensitive to pro-inflammatory stimuli (priming).
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    Identification of human CD4+ T cell populations with distinct antitumor activity
    (American Association for the Advancement of Science, 2020-07-01) Nelson, Michelle H.; Knochelmann, Hannah M.; Bailey, Stefanie R.; Huff, Logan W.; Bowers, Jacob S.; Majchrzak-Kuligowska, Kinga; Wyatt, Megan M.; Rubinstein, Mark P.; Mehrotra, Shikhar; Nishimura, Michael I.; Armeson, Kent E.; Giresi, Paul G.; Zilliox, Michael J.; Broxmeyer, Hal E.; Paulos, Chrystal M.; Microbiology and Immunology, School of Medicine
    How naturally arising human CD4+ T helper subsets affect cancer immunotherapy is unclear. We reported that human CD4+CD26high T cells elicit potent immunity against solid tumors. As CD26high T cells are often categorized as TH17 cells for their IL-17 production and high CD26 expression, we posited these populations would have similar molecular properties. Here, we reveal that CD26high T cells are epigenetically and transcriptionally distinct from TH17 cells. Of clinical importance, CD26high and TH17 cells engineered with a chimeric antigen receptor (CAR) regressed large human tumors to a greater extent than enriched TH1 or TH2 cells. Only human CD26high T cells mediated curative responses, even when redirected with a suboptimal CAR and without aid by CD8+ CAR T cells. CD26high T cells cosecreted effector cytokines, produced cytotoxic molecules, and persisted long term. Collectively, our work underscores the promise of CD4+ T cell populations to improve durability of solid tumor therapies.
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    Mechanisms of Gene Regulation by Soy Peptide Lunasin in Innate Immune Cells
    (Office of the Vice Chancellor for Research, 2015-04-17) Casiano-Rivera, Félix M.; Tung, Chun-Yu; Chang, Hua-Chen
    Lunasin is a seed peptide containing 43 amino acids, originally isolated from soybeans. Recently, a novel function of lunasin was discovered, as it acts as an immune modulating agent regulating gene expression of various innate immune cells. Lunasin strongly activated the expression of genes encoding for type I interferon and inflammatory cytokines. Nonetheless, the molecular mechanisms of lunasin’s gene regulation are relatively unknown. Our current hypothesis states that lunasin is able to induce activation of various transcription factors, resulting in gene expression in immune cells. Human dendritic cells (DCs) or monocytes were purified from peripheral blood mononuclear cells (PBMCs) in order to determine the activation of transcription factors. Phosphorylation of STAT1 and NF-ĸB (p65) were evident in cells treated with lunasin using flow cytometry and Western blotting. The results will ultimately lead to the signaling pathways involved in gene expression regulated by lunasin in innate immune cells. By defining the signaling pathway of lunasin, we can have a better understanding of its application in immune modulation.
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    Role of inflammatory cells in pathophysiology and management of diabetic retinopathy
    (Elsevier, 2022-11) Kovoor, Elias; Chauhan, Sunil K.; Hajrasouliha, Amir; Ophthalmology, School of Medicine
    Diabetic retinopathy (DR) is a sight-threatening complication of diabetes mellitus. Several inflammatory cells and proteins, including macrophages and microglia, cytokines, and vascular endothelial growth factors, are found to play a significant role in the development and progression of DR. Inflammatory cells play a significant role in the earliest changes seen in DR including the breakdown of the blood retinal barrier leading to leakage of blood into the retina. They also have an important role in the pathogenesis of more advanced stage of proliferative diabetic retinopathy, leading to neovascularization, vitreous hemorrhage, and tractional retinal detachment. In this review, we examine the function of numerous inflammatory cells involved in the pathogenesis, progression, and role as a potential therapeutic target in DR. Additionally, we explore the role of inflammation following treatment of DR.