Modulation of mast cell proteinase-activated receptor expression and IL-4 release by IL-12.

Abstract

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.

• Authors: Huiyun Zhang, Xiaoyu Yang, Haiwei Yang, Zhongfang Zhang, Qing Lin, Yanshan Zheng, Shaoying Chen, Pingchang Yang, Shaoheng He
• Journal: Immunology and cell biology (Immunol Cell Biol) Vol. 85 Issue 7 Pg. 558-66 (Oct 2007) ISSN: 0818-9641 [Print] United States
• PMID: 17592496 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Butadienes
• Chromones
• Enzyme Inhibitors
• Flavonoids
• Imidazoles
• Morpholines
• Nitriles
• Pyridines
• RNA, Messenger
• Receptors, Proteinase-Activated
• Tyrphostins
• U 0126
• alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide
• Interleukin-12
• Interleukin-4
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• Proto-Oncogene Proteins c-akt
• Extracellular Signal-Regulated MAP Kinases
• Trypsin
• Tryptases
• SB 203580
• 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Topics

• Animals
• Butadienes (pharmacology)
• Cells, Cultured
• Chromones (pharmacology)
• Enzyme Inhibitors (pharmacology)
• Extracellular Signal-Regulated MAP Kinases (antagonists & inhibitors, metabolism)
• Flavonoids (pharmacology)
• Gene Expression Regulation (drug effects)
• Imidazoles (pharmacology)
• Interleukin-12 (pharmacology)
• Interleukin-4 (metabolism)
• Mast Cells (drug effects, metabolism)
• Mice
• Morpholines (pharmacology)
• Nitriles (pharmacology)
• Proto-Oncogene Proteins c-akt (antagonists & inhibitors, metabolism)
• Pyridines (pharmacology)
• RNA, Messenger (metabolism)
• Receptors, Proteinase-Activated (genetics, metabolism)
• Trypsin (pharmacology)
• Tryptases (pharmacology)
• Tyrphostins (pharmacology)