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Epidemiology and Pathogenesis of COVID-19
Published in Hanadi Talal Ahmedah, Muhammad Riaz, Sagheer Ahmed, Marius Alexandru Moga, The Covid-19 Pandemic, 2023
Sidrah Tariq Khan, Sagheer Ahmed
Other cells released in the event of a viral infection include inflammatory cytokines; TNF-α, IL-6, 2, and 10, IFN-α/-γ, Granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemotactic protein 3 (MCP3), macrophage inflammatory protein 1-α (MIP 1 α), which have shown enhanced levels after infection with a coronavirus leading to the migration of inflammatory cells in the lungs resulting in ARDS which has a high mortality rate especially in critical patients. Along with cytokines, increased levels of chemokines such as CCL2/MCP1, interferon gamma-induced protein 10 (IP-10), CXCL1 as well as CXCL5 have also been observed. One study carried out a transcriptomic analysis on infected peripheral blood mononuclear cells (PBMCs) and infected cells from the patient’s bronchoal-veolar lavage fluid (BALF) to ascertain host responses. The results showed an upregulation of inflammatory cytokines such as CCL2, CXCL2, CCL8, CXCL1, IL33, CCL3L1 in the BALF and CXCL10, TNFSF10, TIMP1, C5, IL18, AREG, NRG1, IL10 in the PBMCs which led to a cytokine storm in patients causing severe inflammation in the lungs. Moreover, further analysis also revealed activated apoptotic and P53 signaling pathways that could be the reason behind the lymphopenia seen in many severely ill COVID-19 patients [12].
Innate and Adaptive Immune Dysfunction and Necrotizing Enterocolitis
Published in David J. Hackam, Necrotizing Enterocolitis, 2021
Paula Osterhout, Christina S. Kim, Erika C. Claud
Macrophages are mature in terms of numbers and function by midgestation; however, while adult intestinal macrophages exhibit inflammatory anergy and do not secrete cytokines to induce a local inflammatory response, it has been shown that fetal macrophages do express inflammatory cytokines at levels that developmentally decrease toward term (55). TGFβ2 suppresses this inflammatory cytokine production (55). The migration of macrophages to the site of intestinal injury is regulated by the chemokine CXCL5 found in the epithelial and muscular layers of the intestine, which attracts myeloid cells and is also elevated in immature intestinal tissue (56). In contrast, neutrophils have limited chemotactic ability until post-term (57). Thus, intestinal inflammatory infiltrates in preterm infants have a macrophage predominance.
Angiogenesis and Roles of Adhesion Molecules in Psoriatic Disease
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
Asmita Hazra, Saptarshi Mandal
IL8 is directly angiogenic, as it can cause proliferation, survival, protease activation, and capillary tube formation of CXCR1- and CXCR2-expressing endothelial cells and enhances production of MMPs. The pro-angiogenic nature of IL8 is largely related to the Glu-Leu-Arg (ELF) motif immediately proximal to first N-terminal cysteine. ELF-positive CXC chemokines IL8 (CXCL8), ENA78 (CXCL5), GCP2 (CXCL6), and GRO-a, -b, and -c (CXCL1, 2, and 3) are all pro-angiogenic due to ELF. On the other hand, the ELF-negative CXC chemokine platelet factor 4 (CXCL4), Mig (CXCL9), and γ-interferon-inducible protein 10 (CXCL10) are antiangiogenic and block ELF-positive CXC chemokines and related VEGF and FGF actions.
Transcriptomic analysis reveals the regulatory mechanism underlying the indirubin-mediated amelioration of dextran sulfate sodium-induced colitis in mice
Published in Pharmaceutical Biology, 2023
Zhe Liu, Jin-ru Zhang, Yong-xiang Huang, Xue-ying Li, Hai-peng Zhu, Rui-yi Yang, Song Chen
Ulcerative colitis pathogenesis has not been fully elucidated. DSS-induced colitis mouse models are most often used to recapitulate UC in humans and have become indispensable tools for elucidating the pathogenesis and potential therapeutic targets for UC (Eichele and Kharbanda 2017). In this study, the transcriptomic analysis indicated the decreased transcription of the HSP family members and Nr1d1 in DSS-treated mice. Several studies have reported the protective roles of HSP70 (with isoforms Hspa1a and Hspa1b), HSP40 (Dnajb1), and HSP110 (Hsph1) in DSS-induced colitis (Ohkawara et al. 2006; Tanaka et al. 2007; Berthenet et al. 2016). Nr1d1 is an important circadian pathway regulatory gene associated with DSS-induced colitis (Chen et al. 2022). We also identified several upregulated genes, such as chloride channel accessory 4B (Clca4b), Nos2, Prss22/Prss27, and Cxcl5 (ENA78), as well as an upregulated KEGG pathway, namely, IL-17 signalling. The critical role of IL-17 signalling in colitis has previously been documented (Zhang et al. 2006; Ito et al. 2008). CXCL5, a chemokine that is preferentially expressed in the intestinal epithelium of UC patients, mediates neutrophil recruitment (Z'Graggen et al. 1997). Our results suggest that these key molecules are potential therapeutic targets in UC.
CXCL5-mediated accumulation of mature neutrophils in lung cancer tissues impairs the differentiation program of anticancer CD8 T cells and limits the efficacy of checkpoint inhibitors
Published in OncoImmunology, 2022
Francesca Simoncello, Giulia Maria Piperno, Nicoletta Caronni, Roberto Amadio, Ambra Cappelletto, Giulia Canarutto, Silvano Piazza, Silvio Bicciato, Federica Benvenuti
We tested a classical protocol for neutrophil depletion by administration of anti-Ly6G antibodies into KP-OVA bearing mice.4,55 Despite efficient depletion in the blood, a large fraction of neu persisted in lung tumor tissues as previously reported,56 precluding further analysis (Fig S2A-D). We thus turned into gene expression data to identify mechanisms of neu accumulation in KP tumors. We identified three chemokines (Cxcl5, Cxcl16 and Ccl21a) in common between the top 10% highly expressed chemokine genes in isolated KP cells and KP-OVA tumor tissues (Figure 2a). Of these, Cxcl5 that is directly implicated in neu recruitment in various cancer tissues and in inflamed lungs was chosen for subsequent analysis. A 20-fold induction of Cxcl5 transcripts in tumor lung tissues was also confirmed using a gene expression array (Fig S3A). To isolate the source of Cxcl5 we analyzed tumor tissues upon fractionation into CD45 negative and positive cells and in isolated KP cells ex vivo. We found high expression of Cxcl5 primarily in CD45 negative cells in cancer tissues and in KP cells (Figure 2(b,c)). We conclude that murine KP lung tumors express high levels of Cxcl5 by a cancer-cell autonomous mechanism.
Circulating biomarkers of response to immunotherapy and immune-related adverse events
Published in Expert Review of Molecular Diagnostics, 2022
Zachary Garrison, Noah Hornick, Jeffrey Cheng, Rajan P. Kulkarni
CXCL5 is a member of a family of angiogenic chemokines that include CXCL1, CXCL2, CXCL3, CXCL6, CXCL7, and CXCL8. It has long been studied for its role in inflammation and cancer development [80]. More recently, CXCL5 has been identified as a biomarker of TH-17 cell-mediated autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and pemphigus vulgaris [81–83]. This influence on inflammation has also been observed to extend to immune therapy-induced irAEs. A study of advanced melanoma patients on nivolumab identified changes to CXCL5 levels for several types of inflammatory related irAEs including hypophisitis, thyroid dysfunction, adrenal insufficiency, psoriasiform dermatitis, interstitial pneumonia, hepatitis, radiation dermatitis, rheumarthritis, biliary tract disorder, and bursitis, though they did not find a significant trend in their limited sample size [84]. This relationship was also correlated with serum levels of CD163 expressing macrophages. CD163, a receptor found on monocytes [85,86], is linked to CXCL5 via their shared presence on tumor associated macrophages (TAMs). TAM production of CXCL5 [87] is the most rational explanation for the parallel correlation of CXCL5/CD163 and irAEs. CD163+ macrophages are a key component of tumor infiltrating immune cells that produce chemokines associated with cancer development and inflammation [88]. They have already been identified as a marker of autoimmune diseases such as rheumatoid arthritis, pemphigus vulgaris, and bullous pemphigoid [85].