Differential regulation of cysteinyl leukotriene receptor signaling by protein kinase C in human mast cells.

Cysteinyl leukotrienes (cys-LTs) are a group of lipid mediators that are potent bronchoconstrictors, powerful inducers of vascular leakage and potentiators of airway hyperresponsiveness. Cys-LTs play an essential role in asthma and are synthesized as well as activated in mast cells (MCs). Cys-LTs re...

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Autores principales:	Vinay Kondeti, Ernest Duah, Nosayba Al-Azzam, Charles K Thodeti, Joshua A Boyce, Sailaja Paruchuri
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/418e8f2ea42e4812924527b50897c7ea
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spelling	oai:doaj.org-article:418e8f2ea42e4812924527b50897c7ea2021-11-18T08:59:25ZDifferential regulation of cysteinyl leukotriene receptor signaling by protein kinase C in human mast cells.1932-620310.1371/journal.pone.0071536https://doaj.org/article/418e8f2ea42e4812924527b50897c7ea2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23977066/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Cysteinyl leukotrienes (cys-LTs) are a group of lipid mediators that are potent bronchoconstrictors, powerful inducers of vascular leakage and potentiators of airway hyperresponsiveness. Cys-LTs play an essential role in asthma and are synthesized as well as activated in mast cells (MCs). Cys-LTs relay their effects mainly through two known GPCRs, CysLT1R and CysLT2R. Although protein kinase C (PKC) isoforms are implicated in the regulation of CysLT1R function, neither the role of PKCs in cys-LT-dependent MC inflammatory signaling nor the involvement of specific isoforms in MC function are known. Here, we show that PKC inhibition augmented LTD4 and LTE4-induced calcium influx through CysLT1R in MCs. In contrast, inhibition of PKCs suppressed c-fos expression as well MIP1β generation by cys-LTs. Interestingly, cys-LTs activated both PKCα and PKCε isoforms in MC. However, knockdown of PKCα augmented cys-LT mediated calcium flux, while knockdown of PKCε attenuated cys-LT induced c-fos expression and MIP1β generation. Taken together, these results demonstrate for the first time that cys-LT signaling downstream of CysLT1R in MCs is differentially regulated by two distinct PKCs which modulate inflammatory signals that have significant pathobiologic implications in allergic reactions and asthma pathology.Vinay KondetiErnest DuahNosayba Al-AzzamCharles K ThodetiJoshua A BoyceSailaja ParuchuriPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e71536 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Vinay Kondeti Ernest Duah Nosayba Al-Azzam Charles K Thodeti Joshua A Boyce Sailaja Paruchuri Differential regulation of cysteinyl leukotriene receptor signaling by protein kinase C in human mast cells.
description	Cysteinyl leukotrienes (cys-LTs) are a group of lipid mediators that are potent bronchoconstrictors, powerful inducers of vascular leakage and potentiators of airway hyperresponsiveness. Cys-LTs play an essential role in asthma and are synthesized as well as activated in mast cells (MCs). Cys-LTs relay their effects mainly through two known GPCRs, CysLT1R and CysLT2R. Although protein kinase C (PKC) isoforms are implicated in the regulation of CysLT1R function, neither the role of PKCs in cys-LT-dependent MC inflammatory signaling nor the involvement of specific isoforms in MC function are known. Here, we show that PKC inhibition augmented LTD4 and LTE4-induced calcium influx through CysLT1R in MCs. In contrast, inhibition of PKCs suppressed c-fos expression as well MIP1β generation by cys-LTs. Interestingly, cys-LTs activated both PKCα and PKCε isoforms in MC. However, knockdown of PKCα augmented cys-LT mediated calcium flux, while knockdown of PKCε attenuated cys-LT induced c-fos expression and MIP1β generation. Taken together, these results demonstrate for the first time that cys-LT signaling downstream of CysLT1R in MCs is differentially regulated by two distinct PKCs which modulate inflammatory signals that have significant pathobiologic implications in allergic reactions and asthma pathology.
format	article
author	Vinay Kondeti Ernest Duah Nosayba Al-Azzam Charles K Thodeti Joshua A Boyce Sailaja Paruchuri
author_facet	Vinay Kondeti Ernest Duah Nosayba Al-Azzam Charles K Thodeti Joshua A Boyce Sailaja Paruchuri
author_sort	Vinay Kondeti
title	Differential regulation of cysteinyl leukotriene receptor signaling by protein kinase C in human mast cells.
title_short	Differential regulation of cysteinyl leukotriene receptor signaling by protein kinase C in human mast cells.
title_full	Differential regulation of cysteinyl leukotriene receptor signaling by protein kinase C in human mast cells.
title_fullStr	Differential regulation of cysteinyl leukotriene receptor signaling by protein kinase C in human mast cells.
title_full_unstemmed	Differential regulation of cysteinyl leukotriene receptor signaling by protein kinase C in human mast cells.
title_sort	differential regulation of cysteinyl leukotriene receptor signaling by protein kinase c in human mast cells.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/418e8f2ea42e4812924527b50897c7ea
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Differential regulation of cysteinyl leukotriene receptor signaling by protein kinase C in human mast cells.

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