{"id":2673,"date":"2024-08-26T13:08:43","date_gmt":"2024-08-26T17:08:43","guid":{"rendered":"http:\/\/haidut.me\/?p=2673"},"modified":"2024-08-26T13:08:43","modified_gmt":"2024-08-26T17:08:43","slug":"serotonin-5-ht-increases-inflammatory-mediators-il-6-nf-kb-may-cause-atherosclerosis","status":"publish","type":"post","link":"https:\/\/haidut.me\/?p=2673","title":{"rendered":"Serotonin (5-HT) increases inflammatory mediators (IL-6, NF-kB), may cause atherosclerosis"},"content":{"rendered":"<p>The inflammatory interleukins IL-1 and IL-6 are among the most studied biomarkers\/pathways. Their role in &#8220;autoimmune&#8221; conditions is undisputed and some of the top-selling drugs for such conditions are IL-1 and\/or IL-6 blockers. There is also plenty of evidence that those interleukins play a role in other serious conditions, including cancer and various neurological disorders. Another mediator with systemically inflammatory effects is NF-kB, and its role in autoimmune conditions and atherosclerosis is also undisputed. Drugs that block NF-kB are currently being tested for virtually all chronic conditions, including ones where inflammation is not thought to play a direct role (diabetes, Parkinson&#8217;s, infertility, etc). The study below demonstrated that 5-HT robustly increased levels (and mRNA expression) of IL-6 and NF-kB, and as such likely plays a key role in cardiovascular disease (CVD)\u00a0 &#8211; the current top cause of death in developed countries (soon to be overtaken by cancer, where IL-6 and NF-kB also play a key role). Needless to say, the administration of SSRI has the same effects as 5-HT, and their widespread use may explain the ever-rising CVD\/cancer rates even in children (for who SSRI drugs are approved for use). Conversely, the study demonstrated that serotonin antagonists were able to block the inflammatory effects of serotonin, which would make them desirable candidates for preventing and treating CVD, cancer, autoimmune conditions, neurodegenerative diseases, diabetes, etc.<\/p>\n<p><a href=\"https:\/\/doi.org\/10.1161\/01.CIR.102.20.2522\">https:\/\/doi.org\/10.1161\/01.CIR.102.20.2522<\/a><\/p>\n<p>&#8220;&#8230;IL-6 levels in the culture medium of VSMCs were determined by ELISA. IL-6 mRNA accumulation was determined by use of a Quantikine mRNA colorimetric quantification kit. NF-\u03baB activation was tested by gel retardation assay. <span style=\"text-decoration: underline;\"><strong>5-HT induced IL-6 production<\/strong><\/span> by VSMCs <span style=\"text-decoration: underline;\"><strong>in a time- and dose-dependent manner<\/strong><\/span>, <span style=\"text-decoration: underline;\"><strong>with increased IL-6 mRNA accumulation and nuclear factor-\u03baB activation<\/strong><\/span>. The <span style=\"text-decoration: underline;\"><strong>effect of 5-HT on IL-6 production was significantly inhibited by the 5-HT<sub>2<\/sub>\u00a0receptor antagonist ketanserin and the selective 5-HT<sub>2A<\/sub>\u00a0receptor antagonist sarpogrelate<\/strong><\/span>. Conversely, the <span style=\"text-decoration: underline;\"><strong>5-HT<sub>2<\/sub> receptor agonist \u03b1-methyl-5-HT increased IL-6 production<\/strong><\/span>. The protein kinase C (PKC) inhibitor calphostin C, but not the protein kinase A inhibitor KT5720, suppressed 5-HT\u2013induced IL-6 production. The effect of 5-HT was also abolished in PKC-depleted VSMCs after pretreatment with phorbol 12-myristate 13-acetate for 24 hours. 5-HT acts on 5-HT<sub>2A<\/sub>\u00a0receptors and increases IL-6 synthesis in human VSMCs at least partially through a PKC-dependent pathway. These results suggested that <span style=\"text-decoration: underline; color: #ff0000;\"><strong>5-HT may contribute to inflammatory activation of the vessels during atherogenesis<\/strong><\/span>.&#8221;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>The inflammatory interleukins IL-1 and IL-6 are among the most studied biomarkers\/pathways. Their role in &#8220;autoimmune&#8221; conditions&#8230;<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[2],"tags":[192,1860,55,166,239,12,2053,47],"class_list":["post-2673","post","type-post","status-publish","format-standard","hentry","category-science","tag-5-ht","tag-atherosclerosis","tag-cancer","tag-cvd","tag-il-6","tag-inflammation","tag-nf-kb","tag-serotonin","wpcat-2-id"],"_links":{"self":[{"href":"https:\/\/haidut.me\/index.php?rest_route=\/wp\/v2\/posts\/2673","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/haidut.me\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/haidut.me\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/haidut.me\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/haidut.me\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=2673"}],"version-history":[{"count":1,"href":"https:\/\/haidut.me\/index.php?rest_route=\/wp\/v2\/posts\/2673\/revisions"}],"predecessor-version":[{"id":2674,"href":"https:\/\/haidut.me\/index.php?rest_route=\/wp\/v2\/posts\/2673\/revisions\/2674"}],"wp:attachment":[{"href":"https:\/\/haidut.me\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=2673"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/haidut.me\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=2673"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/haidut.me\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=2673"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}