Pathophysiology of asthma
Louis-Philippe Boulet in Applied Respiratory Pathophysiology, 2017
Eosinophils are considered key cells in asthma. Airway eosinophilia is mainly driven by IL-5, which promotes the production of eosinophils in the bone marrow and contributes to the recruitment of eosinophils through the influence of chemokines such as eotaxins 1, 2, and 3 (CCL11, CCL24, and CCL26, respectively); regulated upon activation, normal T cell expressed and secreted (RANTES); macrophage inflammatory protein (MIP)-1α; and arachidonic acid metabolites including cysteinyl leukotrienes and 5-keto eicosatetraenoic acid [36]. This type of cell increases in the bronchial mucosa after an allergic response. Its pro-inflammatory effects result in the liberation of cytokines, such as IL-3, IL-4, IL-5, and IL-13, various basic proteins, chemokines, growth factors, enzymes, and lipid mediators.
Pathophysiology of Atopic Dermatitis and Atopiform Dermatitis
Donald Rudikoff, Steven R. Cohen, Noah Scheinfeld in Atopic Dermatitis and Eczematous Disorders, 2014
A number of eosinophil-attracting cytokines are responsible for the trafficking of these cells to sites of cutaneous inflammation. These include IL-5, IL-8, RANTES, eotaxin, eotaxin-2, eotaxin-3, monocyte chemoattractant protein (MCP)-3, MCP-4 and TNF-α (Lampinen et al. 2004). Th2, mast, and epithelial cells are important sources of many of these mediators, and it is now recognized that eosinophils themselves produce many cytokines and play an important role in immunoregulation. Recently, the pluripotential cytokine macrophage migration inhibitory factor (MIF), which is expressed at higher levels in the skin and blood of patients with AD, has been proposed as a major factor causing eosinophil accumulation in the skin (Yoshihisa et al. 2010).
Lymphocyte homing and immunology of extranodal lymphoid tissues
Franco Cavalli, Harald Stein, Emanuele Zucca in Extranodal Lymphomas, 2008
Allergic insult of the lung leads to a coordinated recruitment of eosinophils. Upon such insult, lung tissue produces the cytokine interleukin-5 (IL-5), along with eotaxin chemokines, which are three closely related chemokines, CCL11,52,53 CCL24,54 and CCL26,55,56 whose only known receptor (as agonists) is CCR3. Eosinophils express CCR3 and specific receptors for IL-5, and functional blockade of either the IL-5 receptor or CCR3 inhibits eosinophil accumulation in lung.57
Astragaloside IV suppresses inflammatory response via suppression of NF-κB, and MAPK signalling in human bronchial epithelial cells
Published in Archives of Physiology and Biochemistry, 2022
Hsi-Lung Hsieh, Shih-Hai Liu, Ya-Ling Chen, Chien-Yi Huang, Shu-Ju Wu
The cytotoxicity of astragaloside IV in BEAS-2B cells was determined using the CCK8 assay. Astragaloside IV did not demonstrate significant cytotoxic effects at concentration ≤100 μM, and subsequent experiments used astragaloside IV at 10–100 μM concentrations (Figure 1(B)). 100 μM astragaloside IV did not also demonstrate significant cytotoxic effects in 10 ng/mL TNF-α or 10 ng/mL TNF-α/IL-4 induced BEAS-2B cells (Figure 1(C)). BEAS-2B cells seeded in 24-well plates, and cells treated with astragaloside IV, and then stimulated with 10 ng/mL TNF-α. The result demonstrated that astragaloside IV could significantly decrease the levels of IL-6, IL-8, MCP-1, and CCL5 compared to TNF-α-activated BEAS-2B cells in a concentration-dependent manner (Figure 1(D–G)). Real-time PCR assays showed that astragaloside IV significantly also decreased IL-6, IL-8, MCP-1, and CCL5 gene expression compared to TNF-α-activated BEAS-2B cells (Figure 2). Previously, researchers found that IL-4 combined with TNF-α could induce eotaxin (CCL11, CCL24 and CCL26) secretions in BEAS-2B cells (Huang et al.2017). In this study, we found that astragaloside IV suppressed the levels of CCL11, CCL24, and CCL26 in TNF-α/IL-4–stimulated BEAS-2B cells (Figure 3(A–C)). Real-time PCR assay also showed that astragaloside IV could significantly reduce CCL11, CCL24, and CCL26 gene expression compared to TNF-α/IL-4–stimulated BEAS-2B cells (Figure 3(D–F)).
IL-33 reduces tumor growth in models of colorectal cancer with the help of eosinophils
Published in OncoImmunology, 2020
Melanie Kienzl, Carina Hasenoehrl, Paulina Valadez-Cosmes, Kathrin Maitz, Arailym Sarsembayeva, Eva Sturm, Akos Heinemann, Julia Kargl, Rudolf Schicho
Eosinophil migration assays were performed using 5 µm trans-well plates (Corning; CLS3387-8EA) as previously described by us.37 In brief, 1 × 105 IL-33 Eos (or IL-5 Eos) were put in the upper well. Supernatant from CT26 cell lines (conditioned for four days) and unconditioned medium was used for chemoattraction in the lower well. Recombinant CCL24 (eotaxin-2; Immunotools; # 11344174) was used as a positive control for eosinophil migration at the indicated concentrations. Eosinophils that migrated to the lower well were enumerated on a FACS Canto (BD Biosciences) as described previously.38
Clinical Severity and Tear Biomarkers, Eosinophil Cationic Protein and CCL23, in Chronic Allergic Conjunctival Diseases
Published in Seminars in Ophthalmology, 2018
Maki Shoji, Jun Shoji, Noriko Inada
This clinical study also evaluated the usefulness of CCL23 expression in tears as a biomarker for AKC/VKC. CCL23 interacts with CCR1 and recruits monocytes, macrophages, and dendritic cells that express CCR1 on their surface.10 Further, CCL23 has been evaluated as a biomarker for certain inflammatory diseases, including rheumatoid arthritis,16 systemic sclerosis,17 and atopic dermatitis.18 In this study, clinical severity scores and tear ECP grades in CCL23-positive patients with AKC/VKC showed high levels in comparison with those in CCL23-negative patients with AKC/VKC. Therefore, CCL23 is thought to be a useful biomarker expressed in tears in response to aggravation by AKC/VKC. In the eosinophilic inflammation associated with the pathophysiology of AKC/VKC, CCR3 expressed on eosinophils has attracted research attention, and CCR11/eotaxin-1, CCR24/eotaxin-2, CCR26/eotaxin-3, and RANTES, which are ligands for CCR3, were examined as eosinophilic chemokines associated with inflammation. In patients with VKC, it has been reported that levels of eotaxin-1 and eotaxin-2 in tears are significantly increased compared with those in controls, so these have also been identified as a biomarker for VKC.13,19 Further, there are reports that eosinophils are inflammatory cells expressing CCR1, and eosinophils express CCL23 in their cytoplasm.20 In accordance with these previous reports, eosinophils are thought to be major inflammatory cells in the vicious cycle of allergic inflammation via CCR1. Therefore, in severe ACD, combined analysis of ECP and CCL23 in tears is thought to be a useful test for assessing allergic inflammation in the conjunctiva. Further investigation of the usefulness of combined analysis of ECP and CCL23 in tears will be necessary for various therapeutic drugs used in the medical treatment of cACD in the future.