{"id":2847,"date":"2025-04-16T05:22:03","date_gmt":"2025-04-16T05:22:03","guid":{"rendered":"https:\/\/medicine.nus.edu.sg\/medphc\/?p=2847"},"modified":"2025-04-16T05:22:03","modified_gmt":"2025-04-16T05:22:03","slug":"a-combination-of-alveolar-type-2-specific-p38a-activation-with-a-high-fat-diet-increases-inflammatory-markers-in-mouse-lungs","status":"publish","type":"post","link":"https:\/\/medicine.nus.edu.sg\/medphc\/publications\/a-combination-of-alveolar-type-2-specific-p38a-activation-with-a-high-fat-diet-increases-inflammatory-markers-in-mouse-lungs\/","title":{"rendered":"A combination of alveolar type 2\u2013specific p38a activation with a high-fat diet increases inflammatory markers in mouse lungs"},"content":{"rendered":"\r\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone  wp-image-2848\" src=\"https:\/\/medicine.nus.edu.sg\/medphc\/wp-content\/uploads\/sites\/33\/2025\/04\/20250319-FW-300x169.jpg\" alt=\"\" width=\"950\" height=\"535\" srcset=\"https:\/\/medicine.nus.edu.sg\/medphc\/wp-content\/uploads\/sites\/33\/2025\/04\/20250319-FW-300x169.jpg 300w, https:\/\/medicine.nus.edu.sg\/medphc\/wp-content\/uploads\/sites\/33\/2025\/04\/20250319-FW-1024x576.jpg 1024w, https:\/\/medicine.nus.edu.sg\/medphc\/wp-content\/uploads\/sites\/33\/2025\/04\/20250319-FW-768x432.jpg 768w, https:\/\/medicine.nus.edu.sg\/medphc\/wp-content\/uploads\/sites\/33\/2025\/04\/20250319-FW.jpg 1280w\" sizes=\"auto, (max-width: 950px) 100vw, 950px\" \/><\/figure>\r\n\r\n\r\n\r\n<p>&nbsp;<\/p>\r\n\r\n\r\n\r\n\r\n\r\n<p><span style=\"font-size: 24pt;\"><strong>Abstract<\/strong><\/span><\/p>\r\n<p>Chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease afflict millions of individuals globally and are significant sources of disease mortality. While the molecular mechanisms underlying such diseases are unclear, environmental and social factors, such as cigarette smoke and obesity, increase the risk of disease development. Yet, not all smokers or obese individuals will develop chronic respiratory diseases. The mitogen-activated protein kinase p38\u03b1 is abnormally active in such maladies, but its contribution, if any, to disease etiology is unknown. To assess whether p38\u03b1 activation <i>per se<\/i> in the lung could impose disease symptoms, we generated a transgenic mouse model allowing controllable expression of an intrinsically active variant, p38\u03b1<sup>D176A+F327S<\/sup>, specifically in lung alveolar type 2 pneumocytes. Sustained expression of p38\u03b1<sup>D176A+F327S<\/sup> did not appear to induce obvious pathological outcomes or to exacerbate inflammatory outcomes in mice challenged with common respiratory disease triggers. However, mice expressing p38\u03b1<sup>D176A+F327S<\/sup> in alveolar type 2 cells and fed with a high-fat diet exhibited increased numbers of airway eosinophils and lymphocytes, upregulated levels of proinflammatory cytokines and chemokines including interleukin-1<b>\u03b2<\/b> and eotaxin, as well as a reduction in levels of leptin and adiponectin within the lung. Neither high-fat diet nor p38\u03b1<sup>D176A+F327S<\/sup> alone induced such outcomes. Perhaps in obese individuals with associated respiratory diseases, elevated p38\u03b1 activity which happens to occur is the factor that promotes their development.<\/p>\r\n<p>&nbsp;<\/p>\r\n<p>Full article:<a href=\"https:\/\/doi.org\/10.1016\/j.jbc.2025.108425\"> https:\/\/doi.org\/10.1016\/j.jbc.2025.108425<\/a><\/p>\r\n\r\n\r\n\r\n<p>&nbsp;<\/p>\r\n","protected":false},"excerpt":{"rendered":"<p>&nbsp; Abstract Chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease afflict millions of individuals globally and are significant sources of disease mortality. While the molecular mechanisms underlying such diseases are unclear, environmental and social factors, such as cigarette smoke and obesity, increase the risk of disease development. Yet, not all smokers or [&hellip;]<\/p>\n","protected":false},"author":9345,"featured_media":2848,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"site-sidebar-layout":"default","site-content-layout":"default","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"default","adv-header-id-meta":"","stick-header-meta":"default","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"set","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"footnotes":""},"categories":[5],"tags":[],"class_list":["post-2847","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-publications"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.4 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>A combination of alveolar type 2\u2013specific p38a activation with a high-fat diet increases inflammatory markers in mouse lungs - Pharmacology<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/medicine.nus.edu.sg\/medphc\/publications\/a-combination-of-alveolar-type-2-specific-p38a-activation-with-a-high-fat-diet-increases-inflammatory-markers-in-mouse-lungs\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"A combination of alveolar type 2\u2013specific p38a activation with a high-fat diet increases inflammatory markers in mouse lungs - Pharmacology\" \/>\n<meta property=\"og:description\" content=\"&nbsp; Abstract Chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease afflict millions of individuals globally and are significant sources of disease mortality. While the molecular mechanisms underlying such diseases are unclear, environmental and social factors, such as cigarette smoke and obesity, increase the risk of disease development. Yet, not all smokers or [&hellip;]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/medicine.nus.edu.sg\/medphc\/publications\/a-combination-of-alveolar-type-2-specific-p38a-activation-with-a-high-fat-diet-increases-inflammatory-markers-in-mouse-lungs\/\" \/>\n<meta property=\"og:site_name\" content=\"Pharmacology\" \/>\n<meta property=\"article:published_time\" content=\"2025-04-16T05:22:03+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/medicine.nus.edu.sg\/medphc\/wp-content\/uploads\/sites\/33\/2025\/04\/20250319-FW.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"1280\" \/>\n\t<meta property=\"og:image:height\" content=\"720\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Woon Fei\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Woon Fei\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"2 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\/\/medicine.nus.edu.sg\/medphc\/publications\/a-combination-of-alveolar-type-2-specific-p38a-activation-with-a-high-fat-diet-increases-inflammatory-markers-in-mouse-lungs\/#article\",\"isPartOf\":{\"@id\":\"https:\/\/medicine.nus.edu.sg\/medphc\/publications\/a-combination-of-alveolar-type-2-specific-p38a-activation-with-a-high-fat-diet-increases-inflammatory-markers-in-mouse-lungs\/\"},\"author\":{\"name\":\"Woon Fei\",\"@id\":\"https:\/\/medicine.nus.edu.sg\/medphc\/#\/schema\/person\/ea3ccd10ab2f2bba51fd804396287cb0\"},\"headline\":\"A combination of alveolar type 2\u2013specific p38a activation with a high-fat diet increases inflammatory markers in mouse lungs\",\"datePublished\":\"2025-04-16T05:22:03+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\/\/medicine.nus.edu.sg\/medphc\/publications\/a-combination-of-alveolar-type-2-specific-p38a-activation-with-a-high-fat-diet-increases-inflammatory-markers-in-mouse-lungs\/\"},\"wordCount\":265,\"publisher\":{\"@id\":\"https:\/\/medicine.nus.edu.sg\/medphc\/#organization\"},\"image\":{\"@id\":\"https:\/\/medicine.nus.edu.sg\/medphc\/publications\/a-combination-of-alveolar-type-2-specific-p38a-activation-with-a-high-fat-diet-increases-inflammatory-markers-in-mouse-lungs\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/medicine.nus.edu.sg\/medphc\/wp-content\/uploads\/sites\/33\/2025\/04\/20250319-FW.jpg\",\"articleSection\":[\"Publications\"],\"inLanguage\":\"en-US\"},{\"@type\":\"WebPage\",\"@id\":\"https:\/\/medicine.nus.edu.sg\/medphc\/publications\/a-combination-of-alveolar-type-2-specific-p38a-activation-with-a-high-fat-diet-increases-inflammatory-markers-in-mouse-lungs\/\",\"url\":\"https:\/\/medicine.nus.edu.sg\/medphc\/publications\/a-combination-of-alveolar-type-2-specific-p38a-activation-with-a-high-fat-diet-increases-inflammatory-markers-in-mouse-lungs\/\",\"name\":\"A combination of alveolar type 2\u2013specific p38a activation with a high-fat diet increases inflammatory markers in mouse lungs - 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