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Exosomes in Cancer Disease, Progression, and Drug Resistance
Published in Vladimir Torchilin, Handbook of Materials for Nanomedicine, 2020
Taraka Sai Pavan Grandhi, Rajeshwar Nitiyanandan, Kaushal Rege
Liu et al. [17] showed that the tumor exosomal RNAs (derived from melanoma and Lewis lung cancer cells) activate TLR3 on alveolar epithelial cells and recruit neutrophils to promote pre-metastatic niche formation. Tumor exosomal RNA content and not tumor RNA content activated lung epithelial TLR3 and induced chemokine production (CXCL1, CXCL2, CXCL5, and CXCL12), recruited neutrophils and promoted the establishment of pre-metastatic niche. Tumor exosomal RNA was shown to be involved in both expression and activation of lung epithelial TLR3. While the tumor exosomal RNA induced the expression of TLR3 by activation of NF-kB and MAPK pathways in the lung epithelial cells, small nuclear RNA content within the tumor exosomes was shown to activate TLR3.
Immune System Imaging
Published in Margarida M. Barroso, Xavier Intes, In Vivo, 2020
Michael J. Hickey, M. Ursula Norman
Granulocyte colony-stimulating factor (G-CSF) and the CXCR4 antagonist plerixafor are therapeutic agents used to restore circulating neutrophil numbers in neutropenic patients (Devi et al., 2013). 2PM has been used to investigate neutrophil behavior in the bone marrow and the effects of these therapeutic agents, making use of LysM-GFP mice as neutrophil reporter mice because of the high expression of GFP in neutrophils in these animals (Kohler et al., 2011; Devi et al., 2013). Under resting conditions, the majority of neutrophils in the bone marrow were found to be nonmotile, with ~30% undergoing slow random migration. Egress from the bone marrow via transmigration into the sinusoidal vasculature was seen only rarely, although neutrophils adjacent to these vessels actively probed their surroundings. However, G-CSF administration induced marked changes in neutrophil behavior within 1–2 hours, increasing the proportion of actively migratory cells as well as the average migration velocity. In response to G-CSF, neutrophils migrated toward the blood vessels and were seen exiting into the bloodstream. This response was dependent on CXCR2, consistent with a role for induction of chemokine ligands including CXCL1 and CXCL2. Notably, CXCR4 antagonism via plerixafor, which also increases circulating neutrophil numbers, did not modulate neutrophil behavior in the bone marrow, indicating that these agents work via distinct mechanisms. These studies also revealed that neutrophils move from the circulation back into the bone marrow space, undergoing recruitment from the bone marrow microvasculature, and that this behavior is blocked by CXCR4 inhibition.
Principles and Biological Pathways to Tissue Regeneration: The Tissue Regenerative Niche
Published in Claudio Migliaresi, Antonella Motta, Scaffolds for Tissue Engineering, 2014
Ranieri Cancedda, Claudia Lo Sicco
The switch from a pro-inflammatory M1 macrophage stage to a pro-resolving M2 stage is crucial for the healing and the regeneration processes. Locally resident cells stimulated by platelet and macrophage-derived factors could have a "feedback like" regulatory activity ofthe M1-M2 switch. Tasso et al. [2012] tested the hypothesis that in an ectopic bone formation murine model, MSC treated with FGF-2 (a factor abundantly present also in the PL) could cause an increased percentage of alternatively activated pro-resolving (CD206+CD51+) M2 macrophages infiltrating the ectopic implants and a decrease in the percentage of infiltrating pro-inflammatory (CD86+CD40+) M1 macrophages. It is known that the secretory pattern of MSC is highly influenced by their microenvironment, and that these cells are very sensitive to inflammatory stimuli [Trento and Dazzi, 2010; Caplan and Correa, 2011; Singer and Caplan, 2011]. Tasso and co-workers [2012] mimicked in vitro the inflammatory environment surrounding the implanted MSC and tested whether this change in the microenvironment could activate specific intracellular pathways and the release of factors possibly involved in the macrophage functional switch. MSC from the bone marrow express high levels of IL-1R-alpha [Ortiz et al., 2007] which activates the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB)-dependent inflammatory pathways leading to enhanced expression of Cyclo Oxygenase 2 (COX-2) and acute phase proteins, such as KC/CXCL1, involved in the control of the angiogenesis process [Scapini et al., 2004], and Lcn-2, controlling the expression of the stromal cell-derived factor-1 (SDF-1), a chemokine with a
Cardiorespiratory fitness and targeted proteomics involved in brain and cardiovascular health in children with overweight/obesity
Published in European Journal of Sport Science, 2023
Abel Plaza-Florido, Maria Rodriguez-Ayllon, Signe Altmäe, Francisco B. Ortega, Irene Esteban-Cornejo
LAT and CXCL1 proteins (from Neurology and Cardiovascular panels) showed the highest mean differences (-1.00 and -1.04 NPX values respectively; A 1 NPX value difference means a doubling of protein concentration) between fit and unfit groups (downregulated in plasma of fit compared to unfit children with OW/OB). LAT (Linker for activation of T-cells family member 1) is part of the T-cell receptor complex (TCR). It works as an integrator node of several signalling pathways regulating T cell activation (Bartelt & Houtman, 2013). In this context, obesity is characterized by chronic “over-activation” of the immune system, which is reflected by altered T cell activity and infiltration in adipose tissue contributing to systemic low-grade chronic inflammation (Wang et al., 2021). Thus, we could hypothesize that lower levels of LAT in plasma of fit compared to unfit children with OW/OB could be indicative of a lower chronic “over-activation” of the immune system. In the brain health context, an experiment in the zebrafish model showed that LAT could impact early neurogenesis (Loviglio et al., 2017). LAT suppression was associated with increasing brain cells number and size. Conversely, LAT overexpression was associated with decreased cell proliferation in the brain and microcephaly in zebrafish (Loviglio et al., 2017). CXCL1 (C-X-C Motif Chemokine Ligand 1) is involved in the immune- inflammatory response (i.e. contribute to attracting immune cells into injury sites) (Wang et al., 2018), and higher CXCL1 levels in plasma were associated with more adiposity in young adults (Klevebro et al., 2021). Childhood obesity is characterized by a systemic low-grade inflammation that is related to a higher risk of CVD (Barton, 2012; Ortega et al., 2016). In this context, CXCL1 has been considered a pro-inflammatory chemokine and its neutralization has been proposed as a therapeutic target for CVD treatment (Wang et al., 2018). Interestingly, regular physical activity, which can increase CRF levels, decreased CXCL1 levels in serum of rodents (Jablonski et al., 2020). Our findings suggest that CRF could contribute to reduced CXCL1 levels in plasma of children with OW/OB.