Structure-Function Relationships of IL-8 and its two Neutrophil Receptors: IL-8-RA and IL-8-RB
Richard Horuk in Chemoattractant Ligands and Their Receptors, 2020
In this chapter, we consider how interleukin-8 (IL-8) may interact with cell-surface receptors on neutrophils. It is clear that IL-8, a CXC chemokine, acts on neutrophils through high-affinity binding to at least two types of receptor, called IL-8 receptor A and IL-8 receptor B.1–3 The affinities of these receptors for various chemokines as well as the homology between these two receptors and related receptors from rabbit and mouse are shown in Table 1. Either the A-receptor or the B-receptor can mediate chemotaxis of transformed cells in response to IL-8.4 There is a rather stringent specificity of these receptors in that the B-type receptor binds IL-8, MGSA/gro, NAP-2, and other chemokines with high-affinity, while the A-receptor binds with high-affinity only to IL-83,5,6 (see also References 7–9). Both of these receptors were shown by sequence similarity to be members of a large class of cell-surface receptors with diverse ligands and functions known as the G7, or G-coupled 7-helix, transmembrane receptors (reviewed by Probst et al.10 and Houslay11). Because such receptors are anchored by their seven transmembrane segments into the cell membrane, it is difficult to obtain high-resolution structural information from the receptor side of this interaction. However, such receptors have been modeled (see, for example, Cronet et al.12) on the structure of bacteriorhodop-sin, a protein which has yielded structural information on the disposition of the helices in such 7-helix bundles, from X-ray diffraction of 2-dimensional crystals.13
The Roles and Regulation of Prostaglandins within the Uterus
Robert E. Garfield, Thomas N. Tabb in Control of Uterine Contractility, 2019
Interleukin 8 or neutrophil activating protein 1 is a 72 amino acid protein that is produced in response to inflammation by a number of cell types such as monocytes, fibroblasts, and endothelial cells. It has actions as a chemoattractant and activator of neutrophils. In recent studies we have found that interleukin 8 has no direct action on amnion prostaglandin E2 production. In other cell types interleukin 8 has been shown to enhance arachidonate 5-lipoxygenase activity, although not the release of cellular arachidonate.103 Thus interleukin 8 must be regarded as an addition to the cytokines that may play a significant part in the mechanism of (preterm) labor.
Immune Modulation In Sepsis
Thomas F. Kresina in Immune Modulating Agents, 2020
Interleukin 8 Interleukin 8 (IL-8) is a proinflammatory cytokine that serves as a potent chemoattractant factor and activator of neutrophils; it is produced by many cell types after stimulation by IL-1, TNF, or microbial products such as endotoxin. Its release causes neutrophil degranulation, and priming by TNF seems to enhance IL-8-promoted degranulation [78]. It has been detected in the urine of patients with urinary tract infections [79], and in the cerebrospinal fluid of patients with meningococcal disease [80].
Insights into endotoxin-mediated lung inflammation and future treatment strategies
Published in Expert Review of Respiratory Medicine, 2018
Amlan Chakraborty, Jennifer C. Boer, Cordelia Selomulya, Magdalena Plebanski, Simon G. Royce
The most obvious effect observed with airway inflammation is the recruitment of eosinophils. Th2 lymphocytes release interleukin 5 (IL-5) which attracts, activates, and stimulates eosinophils, therefore, perpetuating the inflammatory response [27]. In inflammatory response, the airway walls become thickened due to hypertrophic and hyperplastic mucus glands as well as infiltration of Mφs, neutrophils, and cytotoxic T lymphocytes (CTLs) as well as proliferation of resident structural cells in the chronic setting [28,29]. Cytokines such as interleukin 8 (IL-8) and TNF-α are released by the inflammatory cells leading to tissue damage and oxidative stress. The entry of an allergen is associated with a complex response in the host as different immune cells play their role in dealing with the allergen. The understanding of the cells and the cytokines they produce can serve as therapeutic targets. Therefore, we need to gain insight on how airway inflammation takes place after allergen entry.
Inhibitory effect of recombinant human CXCL8(3-72)K11R/G31P on atherosclerotic plaques in a mouse model of atherosclerosis
Published in Immunopharmacology and Immunotoxicology, 2019
Yuanhua Qin, Weifeng Mao, Lingmin Pan, Yunliang Sun, Fushun Fan, Ying Zhao, Ying Cui, Xiaoqing Wei, Kazuhiro Kohama, Fang Li, Ying Gao
Atherosclerosis is a pathological process that will induce cardiovascular disease. Recent studies demonstrated that inflammation plays an important role in coronary heart disease, and inflammatory factors are involved in atherosclerosis development [1–8]. Interleukin-8 (IL-8) is an important inflammatory factor and is associated with the development of atherosclerosis [9–12]. High levels of IL-8 are associated with an increased risk of coronary artery disease [13–15]. CXCR1 and CXCR2 are receptors of IL-8, in which CXCR1 also binds to CXCL6/7 but CXCR2 displays higher affinity to IL-8 [16,17]. CXCR2 is a therapeutic target to reduce inflammation [18,19]. CXCL8(3-72)K11R (G31P) is a human IL-8 analog, in which the 11th amino acid (AA) lysine was substituted to arginine, and the 31st AA glycine was substituted to proline [20]. G31P analog has higher affinity to receptors and binds to both CXCR1 and CXCR2 of neutrophils to function in regulating inflammation [21,22]. 0.5 nM G31P can suppress the chemotaxis of neutrophils similar with the levels of 129 nM IL-8/CXCL8 [23]. Some studies reported the roles of CXCL8/G31P on the modulation of inflammation-related angiogenesis and ulcerative colitis [24,25]. However, the role of G31P in atherosclerosis is not defined.
Uptake and molecular impact of aluminum-containing nanomaterials on human intestinal caco-2 cells
Published in Nanotoxicology, 2018
Holger Sieg, Caroline Braeuning, Birgitta Maria Kunz, Hannes Daher, Claudia Kästner, Benjamin-Christoph Krause, Thomas Meyer, Pégah Jalili, Kevin Hogeveen, Linda Böhmert, Dajana Lichtenstein, Agnès Burel, Soizic Chevance, Harald Jungnickel, Jutta Tentschert, Peter Laux, Albert Braeuning, Fabienne Gauffre, Valérie Fessard, Jan Meijer, Irina Estrela-Lopis, Andreas F. Thünemann, Andreas Luch, Alfonso Lampen
The levels of interleukin-8 (IL-8) in cell media were measured using an enzyme-linked immunosorbent assay (ELISA). Primary IL-8 antibody (M801), biotin-conjugated human IL-8 (M802B), recombinant IL-8 cytokine, HRP-Conjugated Streptavidin (N100), SuperBlock blocking buffer, 3,3′,5,5′-tetramethylbenzidine (TMB), tumor necrosis factor alpha (TNF-α) and Tween 20 were obtained from Thermofisher scientific. 20 ng/mL tumor necrosis factor alpha (TNF-α) was used as positive control. Following 24-h incubation with particles, media were collected and frozen at 20 °C until analysis. 96 well microplates (Nunc) were coated with human recombinant IL-8 primary antibodies at 1 µg/mL and incubated overnight at 4 °C. Between each step, wells were washed with PBS-Tween 20 (0.05%). After saturation with SuperBlock for 1 h, samples and standards were added into the wells and incubated at room temperature for 2 h. Biotin-conjugated human IL-8 antibodies (0.1 µg/ml) were then added for 1 h followed by 100 µL of HRP 1:10,000 labeling for 45 min. Finally, 100 µL of the chromogenic substrate TMB was added and the reaction was stopped with 100 µL of H2SO4 (1 M). Plates were read at 405 nm. The concentrations of IL-8 expressed in fold of negative control were calculated against a standard curve prepared in duplicate.
Related Knowledge Centers
- Chemokine
- Epithelium
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- Macrophage
- Weibel–Palade Body
- Gene
- G Protein-Coupled Receptor
- Interleukin 8 Receptor, Alpha
- Interleukin 8 Receptor, Beta