{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T15:36:38Z","timestamp":1782920198425,"version":"3.54.5"},"reference-count":44,"publisher":"Wiley","license":[{"start":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T00:00:00Z","timestamp":1694476800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/N013867\/1"],"award-info":[{"award-number":["MR\/N013867\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Connecting Capabilities Fund Initiative","award":["MR\/N013867\/1"],"award-info":[{"award-number":["MR\/N013867\/1"]}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["MR\/N013867\/1"],"award-info":[{"award-number":["MR\/N013867\/1"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2023,9,12]]},"abstract":"<jats:p>Skeletal muscle of patients with sporadic inclusion body myositis (sIBM) presents with inflammation, including upregulation of inflammatory cytokines such as interferon \u03b3 (IFN\u03b3). Non-inflammatory features are also observed, like the sarcoplasmic accumulation of proteins including TDP-43 and p62. This study aimed to investigate the effect of IFN\u03b3 and interleukin 1-\u03b2 (IL-1\u03b2) on TDP-43 and p62 aggregation in vitro. Primary human myotubes were treated with IL-1\u03b2 (20\u2009ng\/mL) and IFN\u03b3 (750\u2009ng\/mL) separately or combined for 48\u2009hr. Sarcoplasmic TDP-43 aggregates and p62 puncta were assessed using image analysis for size, frequency, and colocalization with each other. Total protein expression of TDP-43, p62 and LC3 was assessed using western blotting. The subcellular localization of TDP-43 was also analyzed using image analysis. Combined IL-1\u03b2 and IFN\u03b3 treatment increased puncta size of p62 compared to control (0.49\u2009\u00b1\u20090.13\u2009\u00b5m2 versus 0.28\u2009\u00b1\u20090.06\u2009\u00b5m2), without affecting puncta frequency or p62 expression but with an increased LC3II\/LC3I ratio, suggesting autophagic alterations. IL-1\u03b2 or IFN\u03b3 did not alter p62 puncta size or frequency, suggesting a combined insult of multiple inflammatory mediators is necessary to cause p62 alterations. IL-1\u03b2 increased p62 protein expression in an autophagy-independent manner. None of the cytokine treatments affected TDP-43 protein expression, size, or frequency of TDP-43 aggregates or localization, suggesting IL-1\u03b2 and IFN\u03b3 may influence TDP-43 processing in human skeletal muscle cells. TDP-43 was localized to the sarcoplasm under control conditions, suggesting this may not be a pathological feature. Overall, sIBM-like TDP-43\/p62 features were not triggered by IL-1\u03b2 and\/or IFN\u03b3.<\/jats:p>","DOI":"10.1155\/2023\/9018470","type":"journal-article","created":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T23:05:12Z","timestamp":1694559912000},"page":"1-13","source":"Crossref","is-referenced-by-count":4,"title":["Influence of Inflammatory Cytokines IL-1\u03b2 and IFN\u03b3 on Sarcoplasmic Aggregation of p62 and TDP-43 in Myotubes"],"prefix":"10.1155","volume":"2023","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4703-6794","authenticated-orcid":true,"given":"Bryony","family":"McCord","sequence":"first","affiliation":[{"name":"Centre for Precision Healthcare, UCL Division of Medicine, University College London, London WC1E 6JF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3124-2294","authenticated-orcid":true,"given":"Richard M.","family":"Day","sequence":"additional","affiliation":[{"name":"Centre for Precision Healthcare, UCL Division of Medicine, University College London, London WC1E 6JF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2019.02.003"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-018-0658-8"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.419"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2013.02.010"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-019-0186-x"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-019-1122-5"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz207"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)91260-Y"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aad4583"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2007.131334"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000192128.13875.1e"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24847"},{"issue":"2","key":"13","first-page":"103","article-title":"Diagnostic value of markers of muscle degeneration in sporadic inclusion body myositis","volume":"30","author":"O. 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