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Pro- and Anti-Inflammatory Cytokine Signaling within 3D Tissue Models
Published in Karen J.L. Burg, Didier Dréau, Timothy Burg, Engineering 3D Tissue Test Systems, 2017
Stephen L. Rego, Tian McCann, Didier Dréau
Interleukin-6 (IL6) is an inflammatory cytokine, which belongs to a superfamily that includes oncostatin M and leukemia inhibitory factor. IL-6 is secreted by monocytes, fibroblasts, B cells, and T cells (Akira et al. 1990). IL6 is critical in inducing fever in response to pathogens. Cellular signaling of IL6 requires binding of IL6 to its receptor (IL6R), which in turn activates the coreceptor glycoprotein 130 (gp130), thus, leading to signaling through the JAK/STAT pathway (Schneiders et al. 2015). Interestingly, the IL6R can be shed from cells by the enzyme tumor necrosis factor converting enzyme (TACE) and modulate the inflammatory response through trans-signaling (Rego et al. 2014). Along with its inflammatory properties, IL6 also acts as an anti-inflammatory factor in muscle (Scheller et al. 2011).
Progress and Road Blocks in the Development of Carbon Nanotubes as Cellular Carriers for Nucleic Acids
Published in Vladimir Torchilin, Mansoor M Amiji, Handbook of Materials for Nanomedicine, 2011
Bridget D. Dolash, Donald E. Bergstrom
CpG ODNs are synthetic oligonucleotides containing a CpG dinucleotide flanked by a sequence optimized to specifically activate toll-like receptor 9 (TLR-9). Upon receptor binding, a signaling cascade activates transcription factors that elicit the immune response.50 CpG ODNs were absorbed onto CNTs functionalized with amine-terminated functional groups through 1,3-dipolar cycloaddition. Delivery of the CpG ODNs by CNTs was carried out in mouse spleenocytes.51 The authors saw an increase in protein expression of interleukin-6 (IL-6) as well as interferon-7 (IN-γ) indicating elicitation of the inflammatory immune response.
COVID-19 pathogenesis and host immune response
Published in Sanjeeva Srivastava, Multi-Pronged Omics Technologies to Understand COVID-19, 2022
Surbhi Bihani, Shalini Aggarwal, Arup Acharjee
Interleukin 6 (IL-6), which has been widely associated with the severity of COVID-19 (J. Zhang et al. 2020), is a pleiotropic cytokine with the ability to induce the production of acute-phase proteins (APP) by liver cells and promote antibody production, T-cell differentiation, and megakaryocyte maturation (Tanaka, Narazaki, and Kishimoto 2014). Furthermore, IL-6 inhibits the production of albumin (responsible for maintaining oncotic pressure of the blood) and induces the production of hepcidin (reduces iron levels in serum by blocking iron transporter—ferroportin— in enterocytes and macrophages) and ferritin (iron-storing blood protein) (Tanaka, Narazaki, and Kishimoto 2014; Edeas, Saleh, and Peyssonnaux 2020). Many of these biological effects of IL-6 corroborate very well with the clinical features of COVID-19. Proteome analysis of sera from severe patients has revealed significant upregulation of APPs like serum amyloid A (SAA), C-reactive protein (CRP), alpha-1-antichymotrypsin, and fibrinogen (D’Alessandro et al. 2020; Shen et al. 2020), suggestive of a hyper-inflammatory state associated with the disease. Coagulation-related abnormalities are a significant risk factor in susceptible patients and can be partly attributed to increased platelet production due to IL-6-induced megakaryocyte maturation (Roncati, Manenti et al. 2020; Biswas and Khan 2020; Al-Samkari et al. 2020; Wool and Miller 2021; Roncati, Ligabue et al. 2020). Markedly decreased serum levels of albumin and iron, also called hypoalbuminemia and hypoferremia, respectively, and high serum levels of hepcidin and ferritin have been associated with disease severity, poor clinical outcomes, and mortality (J. Huang et al. n.d.; Yafei Zhang et al. 2020; Zhao et al. 2020; J. Xia et al. 2019; Nai et al. 2021; Cheng et al. 2020). Excess intracellular iron resulting from high hepcidin levels react with intracellular oxygen, leading to reactive oxygen species (ROS) generation. This may lead to oxidative stress and cellular damage in multiple organs. Interestingly, altered iron homeostasis has been implicated in oxidative cell death called ferroptosis (Ursini and Maiorino 2020), which is crucially involved in neurological disturbances (J.-X. Ren et al. 2020), anosmia (loss of smell) (Dinc et al. 2016), and ageusia (loss of taste) (Osaki et al. 1996), features very commonly manifested in COVID-19.
Interleukin-6 in exhaustive exercises and its correlation to bacteremia: a pilot study
Published in Egyptian Journal of Basic and Applied Sciences, 2023
Amr A. Elgharib, Dalia S. Khalifa, Salma A. Khodeer, Youstina Mohsen, Doaa T. Masallat
Cytokines are signaling low molecular weight proteins produced by a broad range of cells as immune cells, endothelial cells, fibroblasts and various stromal cells to regulate the immunity, inflammation and hematopoiesis [1]. They can be classified into family groups according to the types of secondary and tertiary structure or according to cells that secrete them [2]. Interleukin- 6 (IL-6) is an immunomodulatory cytokine with many physiological actions. It is believed that physical exercises induce spikes of the pro-inflammatory and anti-inflammatory cytokines. Regular moderate physical exercises are required to maintain overall balanced health and psychological status, on the other hand, exhaustive exercise was linked to transient immune-suppression which may be due to the elevated levels of cortisol or inhibitory cytokines after strenuous exercises [3]. In addition, cellular immunity is suggested to be suppressed in response to strenuous exercises [4]. Blood samples isolated from individuals participating in extreme endurance events showed that there was transient bacteremia after the event as reported by S. Gill et al [5]. Epidemiological studies show an association between intensity of physical exercise and severity of the body response to infections [6].
Simvastatin enhanced antimicrobial effect of Ag+ against E. faecalis infection of dentine through PLGA co-delivery submicron particles
Published in Journal of Biomaterials Science, Polymer Edition, 2020
Wei Fan, Mengting Duan, Qing Sun, Bing Fan
For testing the inflammatory response induced by LTA (Sigma-Aldrich Co, St. Louis, USA), 200 μL of RAW-264.7 cells (5 × 105 cells/well) were seeded into each well of a 96-well plate. After 24 h, the medium was replaced with 200 μL pre-mixed solution containing α-MEM and LTA (0, 10, 20, 30, 40, 50 μg/mL). After another 24 h, cell-free supernatants were retrieved and stored at −20 °C. For testing the anti-inflammatory ability of simvastatin, after 24 h culture of RAW-264.7 cell in α-MEM and LTA as above, 200 μL α-MEM with simvastatin (0, 50, 100, 200, 300 μg/mL) replaced the supernatant. After another 24 h, cell-free supernatants were stored at −20 °C. The group cultured with 0.1% DMSO was regarded as the negative control, and the group cultured with only α-MEM was the blank control. For testing the anti-inflammatory ability of particles, the preparation of material extracts and cell culture were performed as described above. After inducing by 20 μg/mL LTA for 24 h, the supernatants were removed and 100 μL α-MEM and extracts were added instead. After another 24 h, cell-free supernatants were stored at −20 °C. The group cultured without extracts was regarded as the negative control, and the group cultured with only α-MEM was the blank control. The concentration of interleukin-beta (IL-1β) and interleukin-6 (IL-6) was determined using enzyme-linked immunosorbent assay kits (ELISA, Neobioscience Technology Company Shenzhen, China). In all cases, IL-1β and IL-6 were tested for 3 times.
Inhibitory effect of particulate matter on toll-like receptor 9 stimulated dendritic cells by downregulating mitogen-activated protein kinase and NF-κB pathway
Published in Journal of Toxicology and Environmental Health, Part A, 2020
Madeeha Arooj, Irshad Ali, Hee Kyoung Kang, Jin Won Hyun, Young-Sang Koh
Antigen-presenting cells secrete an important pro-inflammatory cytokine interleukin 12 (IL-12), also categorized as a T-cell stimulating factor, which orchestrates differentiation of naïve T-cells into CD4 T helper 1 (Th1) cells (Samperio 2010). Interleukin 6 (IL-6) is a multifunctional cell-signaling cytokine, known as anti- and pro-inflammatory cytokine initially recognized to be a stimulatory factor for B-cells (Scheller et al. 2011). Tumor necrosis factor-alpha (TNF-α) is involved in local and systemic infection. Liu et al. (2017) reported the inhibitory effect of TNF-α on viral replication and tumorigenesis. Following exposure to bacterial or viral infections, NF-κB and TNF-α regulate antimicrobial mediators (Abdul Cader et al. 2016).