The gateway theory: How regional neural activation creates a gateway for immune cells via an inflammation amplifier
The inflammation amplifier, a nuclear factor-kappa B (NF-kB)feedback loop in non-immune cells including fibroblasts and endothelial cells, describes how NF-kB-mediated transcriptions are enhanced to induce the inflammation in the presence of signal Tranducer and Activator of Transcription 3 (STAT3)...
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doaj-e7ba815d636946b09e0bce3afddd278d2021-04-02T13:39:00ZengElsevierBiomedical Journal2319-41702013-12-0136626927310.4103/2319-4170.113187The gateway theory: How regional neural activation creates a gateway for immune cells via an inflammation amplifierHideki Ogura0Yasunobu Arima1Daisuke Kamimura2Masaaki Murakami3Laboratory of Developmental Immunology, JST-CREST, Graduate School of Frontier Biosciences, Graduate School of Medicine, and WPI Immunology Frontier Research Center, Osaka University, Osaka, JapanLaboratory of Developmental Immunology, JST-CREST, Graduate School of Frontier Biosciences, Graduate School of Medicine, and WPI Immunology Frontier Research Center, Osaka University, Osaka, JapanLaboratory of Developmental Immunology, JST-CREST, Graduate School of Frontier Biosciences, Graduate School of Medicine, and WPI Immunology Frontier Research Center, Osaka University, Osaka, JapanLaboratory of Developmental Immunology, JST-CREST, Graduate School of Frontier Biosciences, Graduate School of Medicine, and WPI Immunology Frontier Research Center, Osaka University, Osaka, JapanThe inflammation amplifier, a nuclear factor-kappa B (NF-kB)feedback loop in non-immune cells including fibroblasts and endothelial cells, describes how NF-kB-mediated transcriptions are enhanced to induce the inflammation in the presence of signal Tranducer and Activator of Transcription 3 (STAT3) activation. It was originally discovered in rheumatoid arthritis and multiple sclerosis mouse models and has since been shown to be associated with various human diseases and disorders including autoimmune diseases, metabolic syndromes, neurodegenerative diseases, and other inflammatory diseases. The amplifier begins with IL-17, which acts as the main signal to express NF-kB-mediated transcriptions, and IL-6, an NF-kB target, which functions as a fuel for the inflammation amplifier. Indeed, other NF-kB targets including various chemokines also act as effector molecules that cause local accumulation of various immune cells and subsequent inflammation. Through extensive studies in the multiple sclerosis model experimental autoimmune encephalomyelitis, we recently demonstrated that regional neural activation induces excess activation of the inflammation amplifier at specific blood vessels in the fifth lumbar cord, creating a gateway for immune cells to enter the central nervous system (CNS). We thus propose the gateway theory to describe how regional neural activation enables immune cells to enter the CNS from the blood and argue that this theory might provide novel therapeutic targets for inflammatory diseases and disorders.http://www.biomedj.org/article.asp?issn=2319-4170;year=2013;volume=36;issue=6;spage=269;epage=273;aulast=OguraBlood-brain barrierchemokinesgateway theoryinflammation amplifierTh17 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hideki Ogura Yasunobu Arima Daisuke Kamimura Masaaki Murakami |
spellingShingle |
Hideki Ogura Yasunobu Arima Daisuke Kamimura Masaaki Murakami The gateway theory: How regional neural activation creates a gateway for immune cells via an inflammation amplifier Biomedical Journal Blood-brain barrier chemokines gateway theory inflammation amplifier Th17 |
author_facet |
Hideki Ogura Yasunobu Arima Daisuke Kamimura Masaaki Murakami |
author_sort |
Hideki Ogura |
title |
The gateway theory: How regional neural activation creates a gateway for immune cells via an inflammation amplifier |
title_short |
The gateway theory: How regional neural activation creates a gateway for immune cells via an inflammation amplifier |
title_full |
The gateway theory: How regional neural activation creates a gateway for immune cells via an inflammation amplifier |
title_fullStr |
The gateway theory: How regional neural activation creates a gateway for immune cells via an inflammation amplifier |
title_full_unstemmed |
The gateway theory: How regional neural activation creates a gateway for immune cells via an inflammation amplifier |
title_sort |
gateway theory: how regional neural activation creates a gateway for immune cells via an inflammation amplifier |
publisher |
Elsevier |
series |
Biomedical Journal |
issn |
2319-4170 |
publishDate |
2013-12-01 |
description |
The inflammation amplifier, a nuclear factor-kappa B (NF-kB)feedback loop in non-immune cells including fibroblasts and endothelial cells, describes how NF-kB-mediated transcriptions are enhanced to induce the inflammation in the presence of signal Tranducer and Activator of Transcription 3 (STAT3) activation. It was originally discovered in rheumatoid arthritis and multiple sclerosis mouse models and has since been shown to be associated with various human diseases and disorders including autoimmune diseases, metabolic syndromes, neurodegenerative diseases, and other inflammatory diseases. The amplifier begins with IL-17, which acts as the main signal to express NF-kB-mediated transcriptions, and IL-6, an NF-kB target, which functions as a fuel for the inflammation amplifier. Indeed, other NF-kB targets including various chemokines also act as effector molecules that cause local accumulation of various immune cells and subsequent inflammation. Through extensive studies in the multiple sclerosis model experimental autoimmune encephalomyelitis, we recently demonstrated that regional neural activation induces excess activation of the inflammation amplifier at specific blood vessels in the fifth lumbar cord, creating a gateway for immune cells to enter the central nervous system (CNS). We thus propose the gateway theory to describe how regional neural activation enables immune cells to enter the CNS from the blood and argue that this theory might provide novel therapeutic targets for inflammatory diseases and disorders. |
topic |
Blood-brain barrier chemokines gateway theory inflammation amplifier Th17 |
url |
http://www.biomedj.org/article.asp?issn=2319-4170;year=2013;volume=36;issue=6;spage=269;epage=273;aulast=Ogura |
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