dTBP2 attenuates severe airway inflammation by blocking inflammatory cellular network mediated by dTCTP

Dimeric translationally controlled tumor protein (dTCTP), also known as histamine-releasing factor, amplifies allergic responses and its production has been shown to increase in inflammatory diseases such as allergic asthma. Despite the critical role of dTCTP in allergic inflammation, little is know...

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Autores principales:	Hyunsoo Cho, Hyo Kyeong Kim, Areum Oh, Mi Gyeong Jeong, Jiseo Song, Kyunglim Lee, Eun Sook Hwang
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Airway epithelial cell Cellular network Mast cell dTBP2 dTCTP Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/b1b5afd936074c359d9924bb2c3b3b6a
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spelling	oai:doaj.org-article:b1b5afd936074c359d9924bb2c3b3b6a2021-11-14T04:29:36ZdTBP2 attenuates severe airway inflammation by blocking inflammatory cellular network mediated by dTCTP0753-332210.1016/j.biopha.2021.112316https://doaj.org/article/b1b5afd936074c359d9924bb2c3b3b6a2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221011008https://doaj.org/toc/0753-3322Dimeric translationally controlled tumor protein (dTCTP), also known as histamine-releasing factor, amplifies allergic responses and its production has been shown to increase in inflammatory diseases such as allergic asthma. Despite the critical role of dTCTP in allergic inflammation, little is known about its production pathways, associated cellular networks, and underlying molecular mechanisms. In this study, we explored the dTCTP-mediated inflammatory networks and molecular mechanisms of dTCTP associated with lipopolysaccharides (LPS)-induced severe asthma. LPS stimulation increased dTCTP production by mast cells and dTCTP secretion during degranulation, and extracellular dTCTP subsequently increased the production of pro-inflammatory molecules, including IL-8, by airway epithelial cells without affecting mast cell activation. Furthermore, dimeric TCTP-binding peptide 2 (dTBP2), a dTCTP inhibitor peptide, selectively blocked the dTCTP-mediated signaling network from mast cells to epithelial cells and decreased IL-8 production through IkB induction and nuclear p65 export in airway epithelial cells. More importantly, dTBP2 efficiently attenuated LPS-induced severe airway inflammation in vivo, resulting in decreased immune cell infiltration and IL-17 production and attenuated dTCTP secretion. These results suggest that dTCTP produced by mast cells exacerbates airway inflammation through activation of airway epithelial cells in a paracrine signaling manner, and that dTBP2 is beneficial in the treatment of severe airway inflammation by blocking the dTCTP-mediated inflammatory cellular network.Hyunsoo ChoHyo Kyeong KimAreum OhMi Gyeong JeongJiseo SongKyunglim LeeEun Sook HwangElsevierarticleAirway epithelial cellCellular networkMast celldTBP2dTCTPTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 144, Iss , Pp 112316- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Airway epithelial cell Cellular network Mast cell dTBP2 dTCTP Therapeutics. Pharmacology RM1-950
spellingShingle	Airway epithelial cell Cellular network Mast cell dTBP2 dTCTP Therapeutics. Pharmacology RM1-950 Hyunsoo Cho Hyo Kyeong Kim Areum Oh Mi Gyeong Jeong Jiseo Song Kyunglim Lee Eun Sook Hwang dTBP2 attenuates severe airway inflammation by blocking inflammatory cellular network mediated by dTCTP
description	Dimeric translationally controlled tumor protein (dTCTP), also known as histamine-releasing factor, amplifies allergic responses and its production has been shown to increase in inflammatory diseases such as allergic asthma. Despite the critical role of dTCTP in allergic inflammation, little is known about its production pathways, associated cellular networks, and underlying molecular mechanisms. In this study, we explored the dTCTP-mediated inflammatory networks and molecular mechanisms of dTCTP associated with lipopolysaccharides (LPS)-induced severe asthma. LPS stimulation increased dTCTP production by mast cells and dTCTP secretion during degranulation, and extracellular dTCTP subsequently increased the production of pro-inflammatory molecules, including IL-8, by airway epithelial cells without affecting mast cell activation. Furthermore, dimeric TCTP-binding peptide 2 (dTBP2), a dTCTP inhibitor peptide, selectively blocked the dTCTP-mediated signaling network from mast cells to epithelial cells and decreased IL-8 production through IkB induction and nuclear p65 export in airway epithelial cells. More importantly, dTBP2 efficiently attenuated LPS-induced severe airway inflammation in vivo, resulting in decreased immune cell infiltration and IL-17 production and attenuated dTCTP secretion. These results suggest that dTCTP produced by mast cells exacerbates airway inflammation through activation of airway epithelial cells in a paracrine signaling manner, and that dTBP2 is beneficial in the treatment of severe airway inflammation by blocking the dTCTP-mediated inflammatory cellular network.
format	article
author	Hyunsoo Cho Hyo Kyeong Kim Areum Oh Mi Gyeong Jeong Jiseo Song Kyunglim Lee Eun Sook Hwang
author_facet	Hyunsoo Cho Hyo Kyeong Kim Areum Oh Mi Gyeong Jeong Jiseo Song Kyunglim Lee Eun Sook Hwang
author_sort	Hyunsoo Cho
title	dTBP2 attenuates severe airway inflammation by blocking inflammatory cellular network mediated by dTCTP
title_short	dTBP2 attenuates severe airway inflammation by blocking inflammatory cellular network mediated by dTCTP
title_full	dTBP2 attenuates severe airway inflammation by blocking inflammatory cellular network mediated by dTCTP
title_fullStr	dTBP2 attenuates severe airway inflammation by blocking inflammatory cellular network mediated by dTCTP
title_full_unstemmed	dTBP2 attenuates severe airway inflammation by blocking inflammatory cellular network mediated by dTCTP
title_sort	dtbp2 attenuates severe airway inflammation by blocking inflammatory cellular network mediated by dtctp
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/b1b5afd936074c359d9924bb2c3b3b6a
work_keys_str_mv	AT hyunsoocho dtbp2attenuatessevereairwayinflammationbyblockinginflammatorycellularnetworkmediatedbydtctp AT hyokyeongkim dtbp2attenuatessevereairwayinflammationbyblockinginflammatorycellularnetworkmediatedbydtctp AT areumoh dtbp2attenuatessevereairwayinflammationbyblockinginflammatorycellularnetworkmediatedbydtctp AT migyeongjeong dtbp2attenuatessevereairwayinflammationbyblockinginflammatorycellularnetworkmediatedbydtctp AT jiseosong dtbp2attenuatessevereairwayinflammationbyblockinginflammatorycellularnetworkmediatedbydtctp AT kyunglimlee dtbp2attenuatessevereairwayinflammationbyblockinginflammatorycellularnetworkmediatedbydtctp AT eunsookhwang dtbp2attenuatessevereairwayinflammationbyblockinginflammatorycellularnetworkmediatedbydtctp
_version_	1718430036789297152

dTBP2 attenuates severe airway inflammation by blocking inflammatory cellular network mediated by dTCTP

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