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Host Response to Biomaterials
Published in Claudio Migliaresi, Antonella Motta, Scaffolds for Tissue Engineering, 2014
Sangeetha Srinivasan, Julia E. Babensee
TLRs are expressed on various cell types including DCs, MOs, T-cells, B-cells, fibroblasts, and ECs.56 TLRs have the ability to specifically recognize pathogen components or pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS), teichoic acids, lipoprotein, "double stranded" RNA (dsRNA), bacterial DNA, and flagellin.11'56,64 TLRs 1, 2, 4, 5, and 6 are expressed on the cell surface, while TLRs 3, 7, 8, and 9 are expressed on intracellular compartments, these receptors facilitate the internalization of antigen and trigger subsequent cellular responses.56 Crucial endogenous ligands of TLRs known as damage-associated molecular patterns (DAMPs) or "danger signals" initiate inflammatory responses upon cell death or tissue damage and act as natural adjuvants. Important DAMPs are endogenous molecules that are normally "hidden self" and released upon cell damage or tissue death such as high-mobility group box protein-1 (HMGB1), heat-shock proteins, and mRNA; or upon tissue damage such as heparan sulfate and fibrinogen.49 The ligation of intracellular TLRs leads to the downstream signaling of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and mitogen-activated protein kinase activation via a MyD88-dependent pathway.56,65 TLRs 3 and 4 can activate the transcription factor IFN regulating factor 3 in a MyD88-independent manner. This results in the generation of IFN-b and IFN-inducible gene products.66 NF-kB, also, participates in gene regulation in the MyD88-independent pathway of TLR signaling.11
Immune Reactions in the Delivery of RNA Interference-Based Therapeutics: Mechanisms and Opportunities
Published in Raj Bawa, János Szebeni, Thomas J. Webster, Gerald F. Audette, Immune Aspects of Biopharmaceuticals and Nanomedicines, 2019
Kaushik Thanki, Emily Falkenberg, Monique Gangloff, Camilla Foged
Over the course of evolution, the immune system has developed to recognize danger signals, i.e., pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), via pattern-recognition receptors (PRRs) [42–44]. Components of RNAi therapeutics, e.g., siRNA, cationic lipids and polymers, may also be recognized by PRRs, which are either membrane-bound, i.e., TLRs and C-type lectin receptors (CLRs), or cytoplasmic receptors viz. NOD-like receptors (NLRs) and RIG-I-like receptors (RLRs) [44]. The following section focuses on the immunological reactions that can occur during RNAi therapy.
Ferruginous bodies exert a strong proinflammatory effect
Published in Journal of Toxicology and Environmental Health, Part A, 2023
Violetta Borelli, Martina Zangari, Annalisa Bernareggi, Fabrizio Bardelli, Francesca Vita, Giuliano Zabucchi
Aside from many other compounds, ferritin and amyloid structures are members of damage associated molecular pattern (DAMP) (Comish et al. 2020; Fukuda et al. 2022; Gong et al. 2020; Roh and Sohn 2018), endogenous danger molecules that, when released from damaged cells, activate the innate immune system by interacting with their receptors on inflammatory cells to trigger enzyme release together with a cytokine “storm.” This phenomenon is believed to result in various inflammatory diseases including severe ocular disease, rheumatoid arthritis, Alzheimer’s disease, atheroscerosis, Parkinson’s disease, systemic lupus erythematosus and cancer. On this basis it was hypothesized that ABs may act as a DAMP (Comish et al. 2020).
Nanoprotection from SARS-COV-2: would nanotechnology help in Personal Protection Equipment (PPE) to control the transmission of COVID-19?
Published in International Journal of Environmental Health Research, 2023
Zhi Xin Phuna, Bibhu Prasad Panda, Naveen Kumar Hawala Shivashekaregowda, Priya Madhavan
Polymers and inorganic materials are excellent to be incorporated into facemasks, bio-based components can also be used to develop effective nanofilters. The use of natural product has always been the choice of interest for the pharmaceutical industry due to their relatively lower extend of adverse side effects. Since the potential therapy for COVID-19 are still under investigation with unknown side effects, natural products have attracted insightful attention. Bailly and Vergoten (2020) have recently reviewed the potential therapy of glycyrrhizic acid (GLR) against SARS-CoV-2 (Bailly and Vergoten 2020). GLR is a triterpenoid saponin that is mainly isolated from the root of the plants Glycyrrhiza glabra (also known as European licorice) (Pastorino et al. 2018). At a membrane level, GLR can stimulate cholesterol-dependent disorganization of lipid rafts that is essential for the entry of coronavirus. Whereas at subcellular level, GLR can trap the high mobility group box 1 (HMGB1) protein that play important roles in COVID-19 pathogenesis (Bailly and Vergoten 2020). As a damage-associated molecular pattern (DAMP) molecule, HMG1 can induce inflammation by triggering TLR4 to generate pro-inflammatory cytokines. HMGB1 also can form complexes with DNA, RNA, or other DAMP molecules, which are then endocytosed by receptor for advanced glycation end products (RAGE) that are only highly expressed in lungs. However, RAGE is disrupted by high levels of HMBG1. Thus, it is believed that SARS-CoV-2 may reach the cellular cytosol via HMGB1-assisted transfer with lysosome leakage (Andersson et al. 2020). Serum level of HMGBI was found to be elevated in COVID-19 patients, where it could induce the expression of SARS-CoV-2 entry receptor ACE2 (Chen et al. 2020). Targeting HMGB1 has emerged as one of the potential therapies against COVID-19.