TY - JOUR
T1 - Differential mRNA expression of prostaglandin receptor subtypes in macrophage activation
AU - Hubbard, Neil
AU - Lee, S. H.
AU - Lim, D.
AU - Erickson, Kent L
PY - 2001
Y1 - 2001
N2 - Assessing the regulation of macrophage receptors for prostaglandin (PGE2) is essential to understanding the control which that potent lipid mediator has in modulating macrophage activities. The purpose of this study was to assess the differential mRNA expression of PGE2 receptor subtypes (EP) during macrophage exposure to activating and transducing agents. RAW 264.7 macrophages constitutively expressed mRNA for EP2, EP3 and EP4 receptor subtypes. Messenger RNA for EP4 was expressed at a much higher level when compared to EP2 in unstimulated macrophages as assessed by kinetic quantitative RT-PCR. When macrophages were stimulated with LPS, EP2 mRNA levels were 12-fold higher when compared to unstimulated macrophages, while EP4 mRNA remained unchanged. Conversely, mRNA levels of both EP2 and EP4 receptors were lower after macrophages were treated with IFN-γ. Messenger RNA levels of both receptors were lower in macrophages after treatment with PGE2 or dibutyryl (db) cAMP. Addition of the PKA inhibitor H89 reversed the effects of PGE2 and dbcAMP to varying degrees. Proteosome and p38 MAP kinase inhibitors blocked the LPS-stimulated increase in EP2 mRNA levels. Those inhibitors had no effect on EP4 mRNA. Thus, activating agents such as LPS and IFN-γ may differentially regulate mRNA for PGE2 receptor types in macrophages but the ligand and its associated signal transducing factors probably have similar regulatory effects.
AB - Assessing the regulation of macrophage receptors for prostaglandin (PGE2) is essential to understanding the control which that potent lipid mediator has in modulating macrophage activities. The purpose of this study was to assess the differential mRNA expression of PGE2 receptor subtypes (EP) during macrophage exposure to activating and transducing agents. RAW 264.7 macrophages constitutively expressed mRNA for EP2, EP3 and EP4 receptor subtypes. Messenger RNA for EP4 was expressed at a much higher level when compared to EP2 in unstimulated macrophages as assessed by kinetic quantitative RT-PCR. When macrophages were stimulated with LPS, EP2 mRNA levels were 12-fold higher when compared to unstimulated macrophages, while EP4 mRNA remained unchanged. Conversely, mRNA levels of both EP2 and EP4 receptors were lower after macrophages were treated with IFN-γ. Messenger RNA levels of both receptors were lower in macrophages after treatment with PGE2 or dibutyryl (db) cAMP. Addition of the PKA inhibitor H89 reversed the effects of PGE2 and dbcAMP to varying degrees. Proteosome and p38 MAP kinase inhibitors blocked the LPS-stimulated increase in EP2 mRNA levels. Those inhibitors had no effect on EP4 mRNA. Thus, activating agents such as LPS and IFN-γ may differentially regulate mRNA for PGE2 receptor types in macrophages but the ligand and its associated signal transducing factors probably have similar regulatory effects.
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U2 - 10.1054/plef.2001.0327
DO - 10.1054/plef.2001.0327
M3 - Article
C2 - 11993722
AN - SCOPUS:0035724880
VL - 65
SP - 287
EP - 294
JO - Prostaglandins Leukotrienes and Essential Fatty Acids
JF - Prostaglandins Leukotrienes and Essential Fatty Acids
SN - 0952-3278
IS - 5-6
ER -