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Vitro Alzheimer’s Disease Modeling Using Stem Cells
Published in Hyun Jung Kim, Biomimetic Microengineering, 2020
Hyun-Ji Park, Song Ih Ahn, Jeong-Kee Yoon, Hyunjung Lee, YongTae Kim
In the AD brain, the continuous increase in Aβ deposition and aggregation induces a chronic reaction of the brain immune system which may lead to severe damage to the brain. These inflammatory responses in the brain are dominated by microglia, primary resident immune cells in the brain (Figure 11.4; Hanisch and Kettenmann 2007). Microglia change their morphological and functional phenotypes to reactive states after detecting Aβ through their pattern recognition receptors including Toll-like receptor 2 (TLR2), TLR4, and TLR6 and their co-receptors such as CD36, CD14, and CD47 (Weggen et al. 2001). These reactive microglia release an excessive amount of pro-inflammatory cytokines, interleukin-1β (IL-1β) family including IL-1β and IL-18, and TNF-α. These pro-inflammatory cytokines consequently induce neurotoxic astrocytes (Liddelow et al. 2017) and cause impaired neuronal function and structural changes, ultimately leading to neuronal death (Heppner, Ransohoff, and Becher 2015, Heneka, Kummer, and Latz 2014, Block, Zecca, and Hong 2007). In addition, microglia, phagocytic immune defenders in the brain, are responsible for removing cellular debris and aggregated proteins. Thus, their impaired phagocytic activity directly contributes to AD development by disrupting the clearance of Aβ or elimination of stressed-but-functional neurons (Brown and Vilalta 2015). In addition, abnormal synaptic pruning in the postnatal brain caused by impaired microglial activity leads to disease progression with synaptic loss (Paolicelli et al. 2011, Schafer et al. 2012).
Clinical Effects of Pollution
Published in William J. Rea, Kalpana D. Patel, Reversibility of Chronic Disease and Hypersensitivity, Volume 5, 2017
William J. Rea, Kalpana D. Patel
To define the degree of systemic inflammation, substances measured are inflammatory mediators such as C-reactive protein, prostaglandin E metabolite, and heat shock protein 60; IL-10 was the selected TH2 anti-inflammatory cytokine. Given that controlled ozone exposures are associated with upregulation of mCD14 on airway macrophages and monocytes, and that a synergistic action on the CD14 effect has been suggested between PM-LPS and ozone,37 they selected mCD14, sCD14, and LPS-binding protein (LBP)38,39 to characterize the LPS-recognition complex components. LPS forms a complex with an acute-phase protein called LBP responsible for the binding and transport of LPS in the circulation.39 A major response to LPS is mediated by its interaction with CD14, a 55-kDa myeloid differentiation antigen that allows endotoxin to interact with the TLR4.39 Finally, TLR4 specifically recognizes LPS and is part of the endotoxin signaling receptor complex that initiates proinflammatory signaling. Since missense mutations such as Asp299Gly are associated with a blunted response to inhaled LPS, it was determined the allelic frequencies of Asp299Gly TLR4 polymorphism in both cohorts and included only children fully capable of responding to LPS.40 Certainly, the chemically sensitive can go down this pathway eventually causing permanent brain damage.
Role of iPSCs in Disease Modeling: Gaucher Disease and Related Disorders
Published in Deepak A. Lamba, Patient-Specific Stem Cells, 2017
Daniel K. Borger, Elma Aflaki, Ellen Sidransky
In addition to dopaminergic neurons, Panicker et al. (9) and Tiscornia et al. (10) also differentiated GD iPSCs into macrophages, by way of monocytes. Both studies used CD14 and CD163 as markers of macrophage differentiation, with Panicker et al. (9) including CD68 and Tiscornia et al. (10) including CD11b and CD33. In all cases, control and GD iPSC lines produced macrophages at similar efficiencies. To further confirm that reduced GCase activity does not impact the iPSC differentiation process, Tiscornia et al. (10) used a lentiviral vector to transduce their type 2 GD iPSC line with wild-type GBA1, which restored GCase activity to control levels. They then compared the differentiation efficiency of both transduced and nontransduced lines and found that both produced cells with similar marker patterns upon differentiation to macrophages (10). Taken together, these results suggest that the metabolic defect in GD has little to no effect on either the reprogramming or the differentiation processes.
Chelidonium majus crude extract induces activation of peripheral blood mononuclear cells and enhances their cytotoxic effect toward HeLa cells
Published in International Journal of Environmental Health Research, 2021
Ana Popovic, Milena Deljanin, Suzana Popovic, Danijela Todorovic, Predrag Djurdjevic, Sanja Matic, Milan Stankovic, Dusko Avramovic, Dejan Baskic
Moreover, the appearance of CD14+ T and B lymphocytes additionally points to the stimulation of the immune response. CD14 is glycoprotein anchored in the membrane via a glycosylphosphatidylinositol (GPI). In certain circumstances, membrane CD14 (mCD14) is shed from the membrane of monocytes/macrophages producing soluble form (sCD14) which can be immanent in large quantities in the human serum and other bodily fluids such as milk, tears, saliva, etc. CD14, abundantly expressed on the surface of monocytes/macrophages, was considered as a marker of this population of cells. Later on, CD14 was found to be expressed in other types of cell as well, dendritic cells, neutrophils, and non-myeloid lineage cells. At first, the expression of CD14 on B and T lymphocytes was attributed to binding of sCD14 to the membrane of these cells, but further studies proved that both B and T lymphocytes can express mCD14. The study of Filipp et al. (2001) showed that sCD14 binding to the surface of B cells induces their growth and differentiation. Arias et al. (2000) reported that the binding of soluble CD14 to lymphocytes resulted in higher IgG1 production by B cells and in increased CD40L expression on T lymphocytes. On the other hand, Labeta et al. (2011) notified that mCD14 is also expressed and functional in a subset of B lymphocytes, whereas Komai-Koma et al. (2009) ratified that human CD8+ T lymphocytes, after activation by TCR stimulation, express surface CD14. Fridlender et al. (1999) also found that the treatment of PBMNCs with various mitogens results in CD14 expression on activated B and T lymphocytes. In our study, we found high expression of CD14 on T and B cells after treatment with 50 µg/ml and 250 µg/ml CME, but further examinations are needed to determine whether these lymphocytes bind soluble CD14 molecules released by monocytes or whether CME treatment induces expression of mCD14 on lymphocytes. Since the expression of CD14, whether sCD14 or mCD14, on lymphocytes was found to be related to their activation, it may be postulated that a high percentage of CD14+ lymphocytes found in our study is a result of the stimulating effect of CME.