China
Africa
Explore chapters and articles related to this topic
Inhibition of Dermal Fibrosis by Interferons
Published in Brian J. Nickoloff, Dermal Immune System, 2019
Brian Berman, Matthew R. Duncan
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
Published in Marek P. Dabrowski, Barbara K. Dabrowska-Bernstein, Immunoregulatory Role of Thymus, 2019
Marek P. Dabrowski, Barbara K. Dabrowska-Bernstein
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.
Myristicin
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
C. Martins, J. Rueff, A.S. Rodrigues
A few studies have demonstrated an anti-inflammatory effect of myristicin in vitro and in vivo. Lee et al. observed an anti-inflammatory effect of myristicin in RAW 264.7 mouse macrophages, presumably related with its inhibition of nitric oxide, cytokines, chemokines, and growth factors. Myristicin did not reduce the cell viability of RAW 264.7 mouse macrophages at concentrations of up to 50 μM, while it decreased NO production. The anti-inflammatory properties of this compound may be related with its inhibition of NO, IL-6, IL-10, IP-10, MCP-1, MCP-3, GM-CSF, MIP-1α, MIP-1β, and LIF in polyinosinic-polycytidylic acid-stimulated macrophages via the calcium pathway.73
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].
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.
Targeting macrophages: a novel avenue for cancer drug discovery
Published in Expert Opinion on Drug Discovery, 2020
Sahana Kumar, Anujan Ramesh, Ashish Kulkarni
Toll-like receptors (TLRs) that are expressed on leukocytes like macrophages and dendritic cells recognize pathogen-derived molecules and damaged cell products and induce inflammatory responses [66]. Targeting TLRs in macrophages can hence induce a pro-inflammatory phenotype and potentially enhance anti-tumor efficacy [67,68]. Several preclinical studies using TLR agonists targeting different TLRs like TLR3, TLR7/8, and TLR 9 have shown to polarize macrophages into a more Th1 and M1 like phenotype and reducing tumor progression [69–73]. Polyinosinic-polycytidylic acid (Poly ICLC), a double-stranded RNA that is a ligand for TLR 3 is being evaluated in Phase 1/2 clinical studies for various solid tumors (NCT03262103, NCT03721679, NCT01984892) [74]. TLR7 agonists imiquimod and 852A have been evaluated in clinical trials for various cancers and demonstrated good tolerance and potential anti-tumor capacity (NCT00899574, NCT00319748, NCT00095160, NCT00189332, NCT00091689) [75]. The current clinical studies targeting TAMs to improve anti-cancer efficacy have been summarized in Figure 1.