Modulation of mast cell proteinase-activated receptor expression and IL-4 release by IL-12.
It has been recognized that protease-activated receptors (PARs), interleukin (IL)-4 and IL-6 are involved in the pathogenesis of allergic diseases, and that IL-12 plays a role in adaptive immune response. However, little is known of the effect of IL-12 on protease-induced cytokine release from mast cells. In the present study, we examined potential influence of IL-12 on mast cell PAR expression and IL-4 and IL-6 release. The results showed that IL-12 downregulated the expression of PAR-2 and upregulated expression of PAR-4 on P815 cells. It also downregulated expression of PAR-2 mRNA, and upregulated expression of PAR-1, PAR-3 and PAR-4 mRNAs. However, IL-12 enhanced trypsin- and tryptase-induced PAR-2 and PAR-2 mRNA expression. It was observed that IL-12 induced release of IL-4, but reduced trypsin- and tryptase-stimulated IL-4 secretion from P815 cells. PD98059, U0126 and LY294002 not only abolished IL-12-induced IL-4 release but also inhibited IL-12-induced phosphorylation of extracellular signal-regulated kinase and Akt. In conclusion, IL-12 may serve as a regulator in keeping the balance of Th1 and Th2 cytokine production in allergic inflammation.
Zhang
Huiyun
H
The Key Immunopharmacology Laboratory of Guangdong Province, Allergy and Inflammation Research Institute, Shantou University Medical College, Shantou, China.
Yang
Xiaoyu
X
Yang
Haiwei
H
Zhang
Zhongfang
Z
Lin
Qing
Q
Zheng
Yanshan
Y
Chen
Shaoying
S
Yang
Pingchang
P
He
Shaoheng
S
D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D018664:Interleukin-12 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000378:metabolism*; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D044462:Receptors, Proteinase-Activated / Q000235:genetics / Q000378:metabolism*; D014357:Trypsin / Q000494:pharmacology; D053802:Tryptases / Q000494:pharmacology; D020032:Tyrphostins / Q000494:pharmacology
D002070:Butadienes; D002867:Chromones; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D009025:Morpholines; D009570:Nitriles; D011725:Pyridines; D012333:RNA, Messenger; D044462:Receptors, Proteinase-Activated; D020032:Tyrphostins; C113580:U 0126; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D018664:Interleukin-12; D015847:Interleukin-4; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D014357:Trypsin; D053802:Tryptases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one