Kondeti, VinayDuah, ErnestAl-Azzam, NosaybaThodeti, Charles K.Boyce, JoshuaParuchuri, Sailaja2014-03-012013Kondeti, Vinay, Ernest Duah, Nosayba Al-Azzam, Charles K. Thodeti, Joshua A. Boyce, and Sailaja Paruchuri. 2013. “Differential Regulation of Cysteinyl Leukotriene Receptor Signaling by Protein Kinase C in Human Mast Cells.” PLoS ONE 8 (8): e71536. doi:10.1371/journal.pone.0071536. http://dx.doi.org/10.1371/journal.pone.0071536.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:11855840Cysteinyl 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.en-USBiologyBiochemistryLipidsLipid MediatorsMolecular Cell BiologySignal TransductionSignaling in Cellular ProcessesProtein kinase C signalingSignaling PathwaysCalcium-Mediated Signal TransductionMechanisms of Signal TransductionMathematicsStatisticsBiostatisticsMedicineClinical ImmunologyImmunityInflammationPulmonologyAsthmaJournal Article2014-03-0110.1371/journal.pone.0071536