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Scleroderma
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
The interleukin-13 pathway in the skin has also been reported to be involved in diffuse SSc. In particular, a seminal paper reported on the comparison of human and murine scleroderma that demonstrated that IL-13 and CCL2 are disease-specific targets (68). The chemokine gene CCL2 levels highly correlated with mRSS and IL-13 levels.
Convalescent Plasma and Antibody Therapy in COVID-19
Published in Debmalya Barh, Kenneth Lundstrom, COVID-19, 2022
Didem Rıfkı, Eymen Ü. Kılıç, Şükrü Tüzmen
IFNs (IFN-I, IFN-α/β) provide a form of natural antiviral protection during the early stages of viral infection. In the later stages of the disease, the number of proinflammatory interleukins (IL-1 β, IL-6), TNF-α, and C-C motif chemokine ligands (CCL-2, CCL-3, and CCL-5) increase while IFNs decrease. Along with the decreased secretion of IFN, antiviral responses are also hampered by the reduced IFN secretion, which in return is accompanied by a rise in chemokine release attracting a large number of inflammatory cells, such as monocytes and neutrophils. This will result in an excessive inflammatory response. Mononuclear macrophages are activated by the delayed release of IFN-α/β via receptors on their surfaces. CCL2, CCL7, and CCL12, which are monocyte chemoattractants, are released by activated mononuclear macrophages, causing an increase in the number of mononuclear macrophages, which leads to increased levels of proinflammatory cytokines (IL1-, IL-6, and TNF-α) [5].
Innate Immune System in Cardiovascular Diseases
Published in Shyam S. Bansal, Immune Cells, Inflammation, and Cardiovascular Diseases, 2022
Benjamin J. Kopecky, Kory J. Lavine
Stimulation of the sympathetic nervous system triggers the release of adrenaline and noradrenaline, which results in the maturation and emigration of myeloid cells, favors the production of CCR2+ precursors [34, 113, 117], and mobilizes monocytes to the spleen [118]. Classical monocytes are rapidly recruited to the infarct (~50% from a splenic reservoir) via MCP-1 [17, 119, 120]. Splenectomy post-myocardial infarction is protective and limits myocardial inflammation [121]. During this time, there are high levels of inflammatory cytokines such as TNF-α, IL-1β, and IL-6 [122] and proteases [123]. Blockade of monocyte recruitment improves outcomes in murine models of myocardial infarction [124, 125]. CCL2 and CCL7 deficiency inhibits monocyte recruitment post-myocardial infarction and attenuates adverse remodeling [119]. Loss of Nr4a1 (responsible for converting classical to non-classical monocytes) increases classical monocyte and pro-inflammatory macrophage abundance and results in worsening heart function [122]. It is believed that CCR2+ macrophages, monocytes, and neutrophils impact collateral damage to the myocardium and accelerate adverse remodeling [110]. While there is a rapid influx of leukocytes, their persistence within the infarct is short lived (average is 20 hours). Most rapidly infiltrating innate immune cells undergo cell death, with a smaller number of cells exiting the heart and accumulating in the liver, lymph nodes, or spleen [116].
Improving therapeutic resistance: beginning with targeting the tumor microenvironment
Published in Journal of Chemotherapy, 2022
Xiao-ying Guan, Xiao-li Guan, Zuo-yi Jiao
Another study in breast cancer cells showed that anthracycline and cyclophosphamide could promote the production of TNF in endothelial and stromal cells. TNF-α promotes the expression of CXCL1/2 in cancer cells via NF-kB pathway, thereby causing chemotherapy resistance [32]. The chemokine CXCL12 is a ligand for CXCR4, and studies have shown that CXCL12/CXCR4 induces focal adhesion kinase and enhances the transcriptional activity of NF-κB and β-catenin through activation of the ERK and AKT signalling pathways, leading to chemotherapy resistance [6]. CCL2 is an important chemokine that is recruited by immune cells into the TME. Studies have shown that CCL2 is the main cause of resistance to cabazitaxel in prostate cancer cells [119]. Interferon also plays an important role in microenvironment-mediated tumor resistance. In ER(-) and basal-like breast cancer, recombinant IL-17A promotes proliferation and resistance to docetaxel by upregulating phosphorylated ERK1/2 [120].
Prospects of cell chemotactic factors in bone and cartilage tissue engineering
Published in Expert Opinion on Biological Therapy, 2022
Ke Chen, Hui Gao, Yongchang Yao
CCFs were first discovered as they attracted immune cells to the site of inflammation [22]. Subsequent studies showed that CCFs could induce the migration of neural spinal cells [23] and neuronal cells [24]. The growth of tumors in invasive breast cancer is also related to SDF-1 [25]. All these findings aroused increasing interest of researchers to take advantage of CCFs for inflammatory and tumor diseases. CCL2 has been found to be of great significance in a variety of neoplastic diseases. Many studies believe that the CCL2/CCR2 axis is closely related to the progression, survival and metastasis of tumors. Targeting therapy on this signaling axis may provide positive guidance for anticancer therapy [26]. With the progress of tissue engineering strategies, CCFs are widely used for the repair of various tissues. Zamani and his colleagues embedded SDF-1 in poly lactic-co-glycolic acid core-shell particles using coaxial electrospraying technology and injected them into the damaged parts of the myocardium. The results indicated that these particles had an obvious effect on recruiting sufficient mesenchymal stem cells (MSCs) to regenerate the myocardium by releasing SDF-1 in a controlled and sustained manner [27]. Many studies have demonstrated that SDF-1 can be used to recruit MSCs and subsequently promote the regeneration of the myocardium and improve cardiac function [28,29]. Similarly, CCFs such as SDF-1 [30,31] and interleukin-8 (IL-8) [32], have been proven to have encouraging effects on bone/cartilage defect repair in a series of experiments.
A patent review of glutaminyl cyclase inhibitors (2004–present)
Published in Expert Opinion on Therapeutic Patents, 2021
Judite R.M. Coimbra, Jorge A.R. Salvador
CCL2 is a member of the C-C chemokine family and one of the key chemotactic cytokines that regulate migration and infiltration of monocytes with a pivotal role in inflammatory conditions. All members of the CCL2-subfamily are N-terminally modified by a pE-residue and this post-translational modification is fundamental for their bioactivity in vivo, contributing to an efficient receptor interaction and stabilization toward N-terminal proteolytic degradation. Role of the QC activity in CCL2 maturation has been investigated, and isoQC was indicated as the predominant enzyme for this process in vivo [7]. Experimental studies have shown that the inhibition of QC activity significantly reduced the chemoattractant activity of non-modified forms of chemokines and related immune response under inflammatory conditions [7,27]. Moreover, the use of QC/isoQC inhibitors has been shown to modulate the CCL2-mediated liver inflammation in nonalcoholic fatty liver disease in mice [52], and to suppress the progression of inflammation-induced renal dysfunction by hindering the CCL2/CCR2 axis (CCL2 binds primarily to receptor CCR2) [53]. Furthermore, the chemokine domain of CX3CL1 was identified as an additional QC substrate. pE-CX3CL1 binds to the CX3CR1 (fractalkine receptor 1) expressed on the cell surface and activates a signaling process that mediates both adhesion and cell migration in inflammatory processes [11]. The QC-catalyzed N-terminal pE-modification was shown to be required for effective activation of the CX3CL1/CX3CR1 axis.