Virus Wars
Satya Prakash Gupta in Cancer-Causing Viruses and Their Inhibitors, 2014
By far the most universal mechanism by which an oncolytic virus might inhibit an oncogenic virus is via induction of type I IFN, which subsequently puts neighboring cells in an antiviral state (primed or full, depending on the response stage) (Yan and Chen 2012). Not only oncolytic viruses, but virtually any type I IFN inducer should be able to carry out this function. Indeed, in the 1960s, it was observed that culture fluids of certain fungi (P. stoloniferum and P. funiculosum), termed statolon, inhibited plaque formation by VSV, mengovirus, and later also the oncogenic Friend murine leukemia retrovirus (Kleinschmidt et al. 1968). Intraperitoneal statolon injection protected chickens against the lethal neoplastic Marek’s disease virus (MDV), even when given 72 hours after the virus, with the degree of protection correlating with type I IFN levels in the sera of the chickens (Vengris and Mare 1973). Notably, in this model Polyinosinic: polycytidylic acid had no protective effect against MDV, arguing that the quality of antiviral signaling influences the ability to control oncovirus activity—an aspect not studied systematically with oncolytic viruses.
Inhibition of Dermal Fibrosis by Interferons
Brian J. Nickoloff in Dermal Immune System, 2019
In studies of this model, bleomycin, an antineoplastic drug, was initially administered intratracheally once to induce lung fibrosis in Swiss-Webster mice. Mice were then treated daily intramuscularly with either saline or recombinant murine IFN-γ (3.9 × 105 U/mouse) for a period of 14 or 21 days.69,70 IFN-γ was found to significantly reduce bleomycin-induced accumulation of total lung collagen, as measured by hydroxy proline content, after both 14 and 21 days of treatment. Lesions from IFN-γ-treated mice contained fewer collagen fibers and the number of fibroblasts present in the lesion was significnatly reduced. IFN-γ was without effect in the absence of bleomycin, suggesting IFN-γ to have had no effect on in vivo basal fibroblast functions during the 14- and 21-day treatment periods. Interestingly, it has also been reported that intraperitoneal administration of the interferon inducer, polyinosinic-polycytidylic acid, ameliorates bleomycin-induced pulmonary fibrosis in hamsters.71 Since polyinosinic-polycytidylic acid selectively induces IFNs-α and -β, and not IFN-γ, the results of this study may be explained by the effectiveness of IFNs-α and -β to inhibit fibrosis in vivo.
Thymus and Neuro-Endocrine-Immune Regulation of Homeostasis
Marek P. Dabrowski, Barbara K. Dabrowska-Bernstein in Immunoregulatory Role of Thymus, 2019
Mice subjected for 2 h on each day to different environmental conditions, ranging from accessibility to chocolate-chip cookies and sweetened water in their home cages to severe restraint in small plastic boxes, were injected daily with 20 μg of polyinosinic-polycytidylic acid (Poly I:C) for 10 d and the interferon (IFN) serum levels were measured on each day. On day 1, all animals injected with Poly I:C showed IFN levels higher than 200 u. On day 10, however, only Poly I:C and sweet groups of animals demonstrated baseline IFN levels (below 30 u), while the restraint group had a mean level of 295 u. These experimental data reported by N. H. Spector,8 are indicative of environmental modulation of neural and neuroendocrine influence on mouse IFN response to a virus-like agent.
Inhibition of Gap Junction–Mediated Intercellular Communication by Poly(I:C) in Cultured Human Corneal Fibroblasts
Published in Current Eye Research, 2020
Hui Zheng, Ye Liu, Dan Xu, Pingping Liu, Xiuxia Yang, Bing Li, Zimu Cao, Yang Liu, Xiaoshuo Zheng
Viral stromal keratitis is a chronic immunopathologic disease characterized by complex interactions between infiltrating immune cells and resident cells of the cornea.15 Ocular viral infection can lead to irreversible corneal damage as a result of associated neovascularization, scarring, and opacification.16 However, the effects of viral infection on gap junctions in the corneal stroma have remained unclear. Polyinosinic-polycytidylic acid [poly(I:C)], a synthetic analog of viral double-stranded RNA (dsRNA), has been used to study the effects of viral infection on various cell types.17,18 Previous studies have shown that poly(I:C) induces the expression of proinflammatory cytokines, chemokines, and adhesion molecules in human corneal fibroblasts (HCFs).19 In the present study, the effects of poly(I:C) on Cx43 expression and GJIC activity in cultured HCFs were examined. The possible role of microRNAs, oxidative stress, and mitogen-activated protein kinase (MAPK) signaling pathways in the effects of poly(I:C) in these cells were also investigated.
Administration time-dependent effects of poly (I:C) on antioxidant and immune responses along the diurnal time scale in zebrafish
Published in Chronobiology International, 2022
Costanza Guidi, M. Ángeles Esteban, Francisco J. Sánchez-Vázquez, Luisa M. Vera
Polyinosinic:polycytidylic acid [poly (I:C)] is a synthetic analog of double-stranded RNA that mimics viral infections by interacting with the toll-like receptor (TLR) family and by eliciting a strong antiviral response in fish, which suggests that this molecule is used as an effective immunostimulatory adjuvant for mammal (Tewari et al. 2010) and fish (Kavaliauskis et al. 2015) vaccines. Immunostimulants like poly (I:C) contain pathogen-associated molecular patterns (PAMPs) that are recognized by specific receptors in host cells and, thus, trigger the immune response in fish species like zebrafish (Álvarez-Rodríguez et al. 2018). Poly (I:C) also induces oxidative stress in fish (Yue et al. 2018), similarly to the response observed after viral and bacterial infections when phagocytic cells destroy invading microorganisms to cause a respiratory burst that results in ROS formation (Schwarz 1996). ROS are oxidant compounds and are, therefore, counterbalanced by organisms’ antioxidant defenses, which include a network of compartmentalized antioxidative enzymes, such as superoxide dismutases, catalases, glutathione peroxidase glutathione reductases, among others (Staerck et al. 2017).
Combining locoregional CAR-T cells, autologous + allogeneic tumor lysate vaccination and levamisole in treatment of glioblastoma
Published in Immunopharmacology and Immunotoxicology, 2022
Meric A. Altinoz, Alp Ozpinar, Emily Hacker, Aysel Ozpinar
In addition to anatomical barriers, there exist a variety of factors in the GBM microenvironment that cause significant inhibition of immune surveillance. These include the recruitment of regulatory T lymphocytes (Tregs) and immunosuppressive myeloid cells, the increase of immunosuppressive cytokines, and the upregulation of immune checkpoint molecules [13]. One strategy to challenge the immunosuppressive GBM-environment is the co-expression of cytokines by CAR T lymphocytes such as IL-12 and IL-15 [1]. In addition to increasing CD8+ T-cell activation, IL-12 provides a type I T-helper differentiation signal. This aids tumor antigen-specific T-cells modified to synthesize IL-12 last for longer periods in the cancer micromilieu and exert higher efficacy in eradicating malignant cell clones compared to CAR transgenic T lymphocytes alone. Given that a lack of CAR-T cell persistence in vivo is an important impediment to clinical success, investigators have modified CAR-T cells to synthesize and release IL-15, the T lymphocyte survival cytokine, in an activation-dependent manner [14]. Upon recognition of their putative antigen, T lymphocytes engineered to synthesize both IL-15 and IL13Rα2-CAR increased IL-15 production, which augmented the cells’ effector efficacy and their antitumor actions in in vitro and in vivo models of GBM [14]. Systemic application of polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (polyICLC) induces IFN-α and -γ dependent entry of cytotoxic lymphocytes into gliomas through stimulation of CXCL10 expression [15].
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