{"id":43775,"date":"2025-09-20T06:47:08","date_gmt":"2025-09-20T04:47:08","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/09\/20\/dimethyl-itaconate-attenuates-il-1-induced-ivig-resistant-inflammation-in-a-coronary-artery-cell-model-of-kawasaki-disease\/"},"modified":"2025-09-20T06:47:08","modified_gmt":"2025-09-20T04:47:08","slug":"dimethyl-itaconate-attenuates-il-1-induced-ivig-resistant-inflammation-in-a-coronary-artery-cell-model-of-kawasaki-disease","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/09\/20\/dimethyl-itaconate-attenuates-il-1-induced-ivig-resistant-inflammation-in-a-coronary-artery-cell-model-of-kawasaki-disease\/","title":{"rendered":"Dimethyl itaconate attenuates IL-1-induced IVIG-resistant inflammation in a coronary artery cell model of Kawasaki disease"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2025 Sep 16:vkaf245. doi: 10.1093\/jimmun\/vkaf245. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Kawasaki disease (KD) is the most common childhood vasculitis. Approximately 25% of KD patients are refractory to standard intravenous immunoglobulin (IVIG) therapy and frequently develop coronary artery lesions (CAL) that result in long-term complications. Transcriptome studies utilizing blood cells from KD patients and reported animal model studies had identified interleukin (IL)-1\u03b2 as a crucial component of an essential immune pathway in the formation of CAL. We previously reported that high-dose immunoglobulin G (IgG) treatment completely inhibited tumor necrosis factor (TNF)-\u03b1-stimulated inflammatory responses in an in vitro human coronary artery endothelial cells (HCAECs) model. Here, we show that IL-1\u03b2, but not TNF-\u03b1, stimulation markedly induced nuclear protein expression of NF-kappa-B inhibitor zeta (I\u03baB\u03b6) in HCAECs. It is of particular significance that IL-1\u03b2-induced I\u03baB\u03b6 expression is entirely refractory to high-dose IgG treatment. Therefore, I\u03baB\u03b6 may be a critical factor in the IVIG-resistant vascular inflammatory responses in severe KD. Itaconate is a Krebs cycle-derived metabolite with several immunomodulatory effects. Dimethyl itaconate (DI), a membrane-permeable derivative of itaconate, can significantly suppress IL-1\u03b2-induced I\u03baB\u03b6 expression in HCAECs. DI is an analog of dimethyl fumarate (DMF), which is already in clinical use for some diseases. Like DI, DMF suppressed IL-1\u03b2-induced I\u03baB\u03b6 expression and subsequent production of inflammatory cytokines, including IL-6 and G-CSF. This study identified I\u03baB\u03b6 as an essential inflammatory factor in IVIG-resistant inflammatory responses in HCAECs. Immunomodulatory substances, such as DI and\/or DMF, may be therapeutically exploited as a novel drug to alleviate inflammation in severe IVIG-resistant KD patients.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40973123\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20250920004707&amp;v=2.18.0.post9+e462414\">40973123<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkaf245\">10.1093\/jimmun\/vkaf245<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2025 Sep 16:vkaf245. doi: 10.1093\/jimmun\/vkaf245. Online ahead of print. ABSTRACT Kawasaki disease (KD) is the most common childhood vasculitis. Approximately 25% of KD patients are refractory to standard intravenous immunoglobulin (IVIG) therapy and frequently develop coronary artery lesions (CAL) that result in long-term complications. Transcriptome studies utilizing blood cells from KD patients and &#8230; <a title=\"Dimethyl itaconate attenuates IL-1-induced IVIG-resistant inflammation in a coronary artery cell model of Kawasaki disease\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/09\/20\/dimethyl-itaconate-attenuates-il-1-induced-ivig-resistant-inflammation-in-a-coronary-artery-cell-model-of-kawasaki-disease\/\" aria-label=\"Read more about Dimethyl itaconate attenuates IL-1-induced IVIG-resistant inflammation in a coronary artery cell model of Kawasaki disease\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[42,71],"tags":[],"class_list":["post-43775","post","type-post","status-publish","format-standard","hentry","category-publicaciones","category-the-journal-of-immunology"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/43775","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=43775"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/43775\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=43775"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=43775"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=43775"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}