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

• Published in: Immunology and cell biology 2007-10, Vol.85 (7), p.558-566
• Main Authors: Zhang, Huiyun, Yang, Xiaoyu, Yang, Haiwei, Zhang, Zhongfang, Lin, Qing, Zheng, Yanshan, Chen, Shaoying, Yang, Pingchang, He, Shaoheng
• Format: Article
• Language: English
• Subjects: Animals; Butadienes - pharmacology; Cells, Cultured; Chromones - pharmacology; Enzyme Inhibitors - pharmacology; Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors; Extracellular Signal-Regulated MAP Kinases - metabolism; Flavonoids - pharmacology; Gene Expression Regulation - drug effects; IL‐12; IL‐4; Imidazoles - pharmacology; Interleukin-12 - pharmacology; Interleukin-4 - secretion; mast cell; Mast Cells - drug effects; Mast Cells - metabolism; Mice; Morpholines - pharmacology; Nitriles - pharmacology; protease‐activated receptor; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - metabolism; Pyridines - pharmacology; Receptors, Proteinase-Activated - genetics; Receptors, Proteinase-Activated - metabolism; RNA, Messenger - metabolism; trypsin; Trypsin - pharmacology; tryptase; Tryptases - pharmacology; Tyrphostins - pharmacology
• ISSN: 0818-9641; 1440-1711
• DOI: 10.1038/sj.icb.7100085

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.