{"id":33614,"date":"2025-05-29T00:47:58","date_gmt":"2025-05-28T22:47:58","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/05\/29\/tfeb-mediated-pro-inflammatory-response-in-murine-macrophages-induced-by-acute-alpha7-nicotinic-receptor-activationhavisha-h-honwad-on-28-de-may-de-2025-at-1000\/"},"modified":"2025-05-29T00:47:58","modified_gmt":"2025-05-28T22:47:58","slug":"tfeb-mediated-pro-inflammatory-response-in-murine-macrophages-induced-by-acute-alpha7-nicotinic-receptor-activationhavisha-h-honwad-on-28-de-may-de-2025-at-1000","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/05\/29\/tfeb-mediated-pro-inflammatory-response-in-murine-macrophages-induced-by-acute-alpha7-nicotinic-receptor-activationhavisha-h-honwad-on-28-de-may-de-2025-at-1000\/","title":{"rendered":"TFEB-Mediated Pro-inflammatory Response in Murine Macrophages Induced by Acute Alpha7 Nicotinic Receptor Activation\u200bHavisha H Honwad   on 28 de May de 2025 at 10:00"},"content":{"rendered":"<div>\n<p><b>J Leukoc Biol<\/b>. 2025 May 28:qiaf077. doi: 10.1093\/jleuko\/qiaf077. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Transcription factors TFEB and TFE3 are crucial for regulating autophagy, lysosomal biogenesis, and lipid metabolism, and have significant roles in macrophage function and innate immunity. The alpha7 nicotinic acetylcholine receptor (\u03b17nAChR), a ligand-gated Ca2+ channel known for its therapeutic potential in neurological and inflammatory disorders, has been implicated in modulating immune responses by modulating macrophage function. Stimulation of \u03b17nAChR with chemical agonists has been claimed to activate TFEB in pancreatic acinar cells and neurons. However, the impact of \u03b17nAChR activation on TFEB and TFE3 in macrophages remained unknown, posing an important question due to the potential implications for inflammation regulation. This study investigates the effects of acute \u03b17nAChR activation on TFEB-mediated responses in murine macrophages using the specific agonist PNU-282987. We demonstrate that \u03b17nAChR stimulation triggers TFEB nuclear translocation and lysosomal expansion. Surprisingly, PNU-282987 induces a broad pro-inflammatory gene signature without concomitant cytokine secretion, suggesting an uncoupling of gene expression from cytokine release. Mechanistically, TFEB activation requires the lysosomal Ca2+ exporter MCOLN1 and the Ca2+-dependent phosphatase PPP3\/calcineurin. Additionally, PNU-282987 elevates reactive oxygen species (ROS) levels, and ROS are involved in TFEB activation by PNU-282987. Notably, even with \u03b17nAChR deletion, compensatory ROS-mediated TFEB activation persists, suggesting the involvement of additional mechanisms of action for PNU-282987. Our findings reveal a novel \u03b17nAChR-TFEB signaling axis in macrophages, offer new insights into the cholinergic regulation of immune responses, establish a baseline for comparison with disease states, and identify potential therapeutic targets for modulating inflammation.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40435320\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=8405628&amp;ff=20250528184757&amp;v=2.18.0.post9+e462414\">40435320<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jleuko\/qiaf077\">10.1093\/jleuko\/qiaf077<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Leukoc Biol. 2025 May 28:qiaf077. doi: 10.1093\/jleuko\/qiaf077. Online ahead of print. ABSTRACT Transcription factors TFEB and TFE3 are crucial for regulating autophagy, lysosomal biogenesis, and lipid metabolism, and have significant roles in macrophage function and innate immunity. The alpha7 nicotinic acetylcholine receptor (\u03b17nAChR), a ligand-gated Ca2+ channel known for its therapeutic potential in neurological &#8230; <a title=\"TFEB-Mediated Pro-inflammatory Response in Murine Macrophages Induced by Acute Alpha7 Nicotinic Receptor Activation\u200bHavisha H Honwad   on 28 de May de 2025 at 10:00\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/05\/29\/tfeb-mediated-pro-inflammatory-response-in-murine-macrophages-induced-by-acute-alpha7-nicotinic-receptor-activationhavisha-h-honwad-on-28-de-may-de-2025-at-1000\/\" aria-label=\"Read more about TFEB-Mediated Pro-inflammatory Response in Murine Macrophages Induced by Acute Alpha7 Nicotinic Receptor Activation\u200bHavisha H Honwad   on 28 de May de 2025 at 10:00\">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":[86,42],"tags":[],"class_list":["post-33614","post","type-post","status-publish","format-standard","hentry","category-journal-of-leukocyte-biology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/33614","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=33614"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/33614\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=33614"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=33614"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=33614"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}