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      Altered IL-32 Signaling in Abdominal Aortic Aneurysm


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          Introduction and Objective: Interleukin (IL)-32 is a pro-inflammatory cytokine not previously studied in relation to abdominal aortic aneurysm (AAA). The aim of this study was to elucidate the expression and localization of IL-32 in AAA. Methods: Expression and localization of IL-32 in human aortic tissue was studied with immunohistochemical analysis and Western blot (AAA: n = 5; controls: n = 4). ELISA was used to measure IL-32 in human plasma samples (AAA: n = 140; controls: n = 37) and in media from cultured peripheral blood mononuclear cells (PBMCs) from 3 healthy donors. IL-32 mRNA in PBMCs, endothelial cells, aortic smooth muscle cells (SMCs), and aortic tissue samples of AAA ( n = 16) and control aortas ( n = 9) was measured with qPCR. Results: IL-32 was predominantly expressed in SMCs and T-cell-rich areas. Highest mRNA expression was observed in the intima/media layer of the AAA. A weaker protein expression was detected in non-aneurysmal aortas. Expression of IL-32 was confirmed in isolated T cells, macrophages, endothelial cells, and SMCs, where expression was also inducible by cytokines such as interferon-γ. There was no difference in IL-32 expression in plasma between patients and controls. Conclusion: IL-32 signaling is altered locally in AAA and could potentially play an important role in aneurysm development. Further studies using animal models would be helpful to study its potential role in AAA disease.

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          Most cited references 28

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          Blocking IL-1 in systemic inflammation

          A growing number of systemic inflammatory diseases characterized in part by recurrent fevers, leukocytosis, anemia, and elevated acute phase proteins are linked to interleukin (IL)-1 activity since rapid and sustained resolution is observed upon specific blockade of IL-1 receptors. Rapid resolution of systemic and local inflammation is now also reported in systemic onset juvenile idiopathic arthritis (SoJIA). Loss of control of the secretion of IL-1β might be a common mechanism explaining the aberrant activity of IL-1 in these diseases.
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            Understanding the pathogenesis of abdominal aortic aneurysms.

            An aortic aneurysm is a dilatation in which the aortic diameter is ≥3.0 cm. If left untreated, the aortic wall continues to weaken and becomes unable to withstand the forces of the luminal blood pressure resulting in progressive dilatation and rupture, a catastrophic event associated with a mortality of 50-80%. Smoking and positive family history are important risk factors for the development of abdominal aortic aneurysms (AAA). Several genetic risk factors have also been identified. On the histological level, visible hallmarks of AAA pathogenesis include inflammation, smooth muscle cell apoptosis, extracellular matrix degradation and oxidative stress. We expect that large genetic, genomic, epigenetic, proteomic and metabolomic studies will be undertaken by international consortia to identify additional risk factors and biomarkers, and to enhance our understanding of the pathobiology of AAA. Collaboration between different research groups will be important in overcoming the challenges to develop pharmacological treatments for AAA.
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              Identification of a novel gene expressed in activated natural killer cells and T cells.

              We have isolated a cDNA clone from a human activated NK cell-derived cDNA library that identifies a transcript (NK4) that is selectively expressed in lymphocytes. The expression of this transcript is increased after activation of T cells by mitogens or activation of NK cells by IL-2 (lymphokine-activated killer cells). The transcript levels demonstrated by Northern blot analysis increase by 12 h after activation, remain high for at least 48 h, and require protein synthesis for expression. Southern blot analysis of B lymphoblastoid lines derived from 18 unrelated individuals reveal variable banding patterns suggestive of polymorphism within the NK4 gene. No homology was found between the sequence of the coding region of this transcript and any sequences in the GenBank data base. Sequence homology to the U1 small nuclear RNA was found within the 3' untranslated region immediately upstream of the site of polyadenylation, suggesting a possible role for U1 in the polyadenylation process. Sequence analysis indicates the transcript would encode a protein having a mass of 27 kDa. The presence of a signal sequence and lack of a transmembrane region suggests that the protein is secreted. In addition, the protein contains an RGD sequence that may be involved in cellular adhesion. This transcript appears to encode a novel product common to the activation pathways of both NK cells and T cells.

                Author and article information

                J Vasc Res
                Journal of Vascular Research
                S. Karger AG
                July 2020
                20 May 2020
                : 57
                : 4
                : 236-244
                aDivision of Drug Research, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden
                bDivision of Medical Diagnostics, Department of Laboratory Medicine, Jönköping County, Jönköping, Sweden
                cDepartment of Medical Cell Biology, Uppsala University, Uppsala, Sweden
                dDivision of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden
                eDepartment of Surgical Sciences, Section of Vascular Surgery, Uppsala University, Uppsala, Sweden
                Author notes
                *Prof. Dick Wågsäter, Department of Medical Cell Biology, Uppsala University, BOX 571, SE–751 23 Uppsala (Sweden), Dick.wagsater@mcb.uu.se
                507667 J Vasc Res 2020;57:236–244
                © 2020 The Author(s) Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Usage and distribution for commercial purposes requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 5, Pages: 9
                Research Article


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