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Epithelial Cells
Published in Bruce S. Bochner, Adhesion Molecules in Allergic Disease, 2020
RANTES (regulated on activation, normal T-cell expressed and presumably secreted), a member of the C-C chemokine family, is a chemoattractant for eosinophils, basophils, memory T-lymphocytes, and monocytes (170–172). Alam et al. (173) suggested a role for RANTES in the etiology of asthma when they found elevated levels of the chemokine in the BAL fluid of asthmatics compared with that of normal subjects; Venge and coworkers have shown that RANTES and IL-5 are the major eosinophil chemoattractants in the asthmatic lung (174). Marked epithelial expression of RANTES has also been observed in nasal polyps (175). In vitro, unstimulated human bronchial epithelial cells produce little or no RANTES but production is increased in response to IL-1, TNF-α, and IFN-γ (175–177). Glucocorticoids inhibit RANTES synthesis both in vitro (175,176) and in vivo (177).
Biology, Biochemistry and Pathophysiology of the Rantes Chemokine
Published in Richard Horuk, Chemoattractant Ligands and Their Receptors, 2020
Peter J. Nelson, James M. Pattison, Alan M. Krensky
The RANTES chemokine is expressed in a regulated manner during human development. In general, only a few fetal tissues appear to express RANTES. These include megakaryocytes (found in extramedullary hematopoiesis within spleen) and kidney.33 The kidney develops from its core outward. The outer region of the developing kidney is poorly differentiated while the center regions show more defined morphology. When this “developmental gradient” was examined concurrently by in situ hybridization, using RANTES mRNA-specific antisense oligomers, and stained with an anti-RANTES monoclonal antibody, strong expression of RANTES mRNA was found throughout the kidney. Interestingly, no expression of RANTES protein was found in the outer region of the developing organ while the center of the fetal kidney showed increasing levels of RANTES protein. The strongest protein expression was present in the glomerular mesangium and in the proximal tubules. These results indicate both a developmental control and a translational control of RANTES expression in these tissues.33
Therapies to Prevent or Inhibit Chemokine Receptor Expression
Published in Thomas R. O’Brien, Chemokine Receptors and AIDS, 2019
J. Scott Cairns, M. Patricia D’Souza
Five β-chemokine derivatives that bind CCR5 with diminished cellular signaling capabilities have been reported. These are RANTES (9–68) and RANTES (3–68), in which the first 8 or the first 2 N-terminal amino acids of RANTES have been deleted, respectively (75); Met-RANTES, in which a methionine is appended to the N-terminus of RANTES (76); aminooxypentane (AOP)-RANTES (77); and nonanoyl (NNY)-RANTES (78). Additional RANTES derivatives with improved affinity and ability to inhibit HIV replication are also under development (R. Offord, personal communication). Initially, these chemokine derivatives were thought to inhibit HIV by a process of competitive inhibition for viral binding. However, it now appears more likely that the effects on HIV replication are mediated predominantly by inhibitor-mediated coreceptor down-regulation. In support of this hypothesis, AOP-RANTES induces down-regulation of CCR5 (55), whereas MCP-3, which binds to CCR5 with nearly the same affinity as RANTES, fails to induce receptor down-regulation and has negligible effects on HIV replication in vitro (79). AOP-RANTES and NNY-RANTES have been shown to inhibit HIV replication in vivo in SCID mice reconstituted with human peripheral blood cells (hu PBL-SCID mice). Further, NNY-RANTES was able to prevent HIV infection in a subset of hu-PBL mice challenged with an R5 HIV isolate (78). However, in NNY-RANTES-treated mice that became infected on challenge with an R5 virus, HIV emerged that was resistant to the therapeutic agent and exhibited an altered tropism for CXCR4.
The discovery and development of oncolytic viruses: are they the future of cancer immunotherapy?
Published in Expert Opinion on Drug Discovery, 2021
Shunchuan Zhang, Samuel D Rabkin
Chemokines are a family of secreted chemoattractant proteins that mediate immune cell trafficking to influence immune responses, both beneficially and detrimentally, promoting tumorigenesis and/or immunosuppression [106]. OVs have been armed with various chemokines (Table 2). CCL5 (RANTES) is a proinflammatory chemokine recruiting T cells, DCs, macrophages, and NK cells to the TME [106]. An oAd expressing RANTES increased tumors-specific TILs and NK cells and inhibited primary and distal tumors [107]. CCL5 expressing oVV (vvCCL5) had decreased pathogenicity, increased immune cell infiltration (effector CD4 + T cells and DCs), virus in the tumor, and inhibition of tumor growth [108]. vvDD-CCL19 treatment of mouse tumors also resulted in increased DC and effector T cell infiltration and inhibition of tumor growth [109]. In contrast, intravenous injection of oVV expressing CXCL11 (vvDD-CXCL11) was no better than parental vvDD in a subcutaneous model, despite increasing TILs [110], while it greatly extended survival in an intraperitoneal tumor model [111]. OVSV expressing CXCL9 did not increase TILs nor improve inhibition of tumor growth in mouse syngeneic tumors [112].
Severe dengue and liver involvement: an overview and review of the literature
Published in Expert Review of Anti-infective Therapy, 2020
Po Ying Chia, Tun-Linn Thein, Sean Wei Xiang Ong, David Chien Lye, Yee Sin Leo
Dengue infected liver cells secreted increased levels of chemokine ligand 5 also known as Regulated Upon Activation, Normal T cell Expressed and Secreted (RANTES) [47]. The upregulation of RANTES signaling in dengue-infected cells occurred via at least two different pathways, oxidative-stress dependent activation of nuclear factor for IL-6 and oxidant-independent pathway via an unknown factor. RANTES then recruited T cells, monocytes, natural killer cells to sites of infection and inflammation. The final outcome of dengue virus infection of hepatocytes was apoptosis via different pathways, including transcription factor NF-KB activation, endoplasmic reticulum stress-triggered p38 dependent and transcription factor CCAAT-enhancer-binding protein homologous protein-mediated apoptosis as seen in other flaviviruses [48–50].
Exosomes released by breast cancer cells under mild hyperthermic stress possess immunogenic potential and modulate polarization in vitro in macrophages
Published in International Journal of Hyperthermia, 2020
Kacoli Sen, Austin E. F. Sheppe, Ishita Singh, Winnie W. Hui, Mariola J. Edelmann, Carlos Rinaldi
Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) is an inflammatory chemokine released by macrophages, which acts as a chemoattractant for T cells [47]. RANTES is also known to be immunostimulatory for T cells [48] and may lead to enhanced recruitment of T cells. In this study, macrophages, which became stimulated due to treatment with exosomes released by hyperthermia-treated cancer cells, also released more RANTES (Figure 7). The instance of exosomal Hsp70 eliciting a pro-inflammatory response in macrophages has been demonstrated previously but in the context of bacterial infections [49]. The increased immunogenic potential of exosomes secreted by cancer cells posthyperthermia suggests potential role in hyperthermia-based cancer immunotherapies. Keeping in mind the immunogenic antichemotherapeutic potential of hyperthermia-based exosomes, numerous recent studies are focusing on studying the differential expression of exosomal lipids or proteins [50,51]. Probing these hyperthermia-induced antitumorigenic immunostimulatory molecules is pertinent to accomplish a comprehensive understanding of alternative therapies like hyperthermia.