Agonist- and T(H)2 cytokine-induced up-regulation of cysteinyl leukotriene receptor messenger RNA in human monocytes.
BACKGROUND
The cysteinyl leukotrienes (CysLTs) are lipid mediators that have been implicated in the pathogenesis of allergic diseases, and their actions are mediated via specific receptors named CysLT1 receptor (CysLT1R) and CysLT2 receptor (CysLT2R). Little information is known about the role of T(H)2 cytokines in the regulation of both CysLT1R and CysLT2R expression.


OBJECTIVE
To investigate the possible modulation of both CysLT1R and CysLT2R messenger RNA (mRNA) expression, we have developed a real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay based on the TaqMan fluorescence method to quantify CysLT1R and CysLT2R mRNA in human monocytes.


METHODS
Human monocytes were stimulated with leukotriene D4 or interleukin (IL) 4 or IL-13, and the levels of CysLT1R and CysLT2R mRNA were measured by the quantitative RT-PCR.


RESULTS
CysLT1R and CysLT2R mRNA was increased after stimulation with leukotriene D4. CysLT1R mRNA was augmented 150-fold after treatment with IL-4; however, no significant increase was observed in CysLT2R mRNA level. IL-13 could induce a biphasic augmentation of CysLT1R mRNA level. In contrast to IL-4, IL-13 enhanced CysLT2R mRNA level, with a maximal effect at 2 hours of incubation.


CONCLUSIONS
CysLT1R and CysLT2R expression can be regulated by CysLT itself and T(H)2 cytokines at the transcriptional level.
Shirasaki
Hideaki
H
Department of Otolaryngology, Sapporo Medical University, Chuo-ku, Sapporo, Japan. shira@sapmed.ac.jp
Seki
Nobuhiko
N
Fujita
Manabu
M
Kikuchi
Megumi
M
Kanaizumi
Etsuko
E
Watanabe
Kazumasa
K
Himi
Tetsuo
T
D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D020024:Leukotriene Antagonists / Q000494:pharmacology; D017998:Leukotriene D4 / Q000494:pharmacology*; D008565:Membrane Proteins / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D018077:Receptors, Leukotriene / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013189:SRS-A / Q000031:analogs & derivatives / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
C071435:BAY u9773; D016207:Cytokines; D018793:Interleukin-13; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D011422:Propionates; D011804:Quinolines; D012333:RNA, Messenger; D018077:Receptors, Leukotriene; D013189:SRS-A; D015847:Interleukin-4; C059141:verlukast; D017998:Leukotriene D4; C412375:cysteinyl leukotriene receptor 2; C083169:leukotriene D4 receptor