Induction of IL-13 production and upregulated expression of protease activated receptor-1 by RANTES in a mast cell line

Department of Pathophysiology, Hainan Medical College, Haikou, Hainan 571101, China.
Cytokine (Impact Factor: 2.66). 11/2010; 53(2):231-8. DOI: 10.1016/j.cyto.2010.10.005
Source: PubMed


RANTES is a potent chemoattractant for various important inflammatory cells such as eosinophils, memory T cells and mast cells. It has been long recognized as a crucial player in the pathogenesis of allergy. However, little is known of its effects on cytokine secretion and protease activated receptor (PAR) expression in mast cells. In the present study, we examined potential influence of RANTES on IL-13 and IL-12 release from P815 cells and PAR expression on P815 cells by using flow cytometry analysis, quantitative real-time PCR, ELISA and cellular activation of signaling ELISA (CASE) techniques. The results showed that RANTES induced up to 2.2-fold increase in IL-13, but not IL-12 release from P815 cells. Blocking antibodies against RANTES and CCR5 diminished RANTES induced IL-13 release. Furthermore, RANTES upregulated expression of PAR-1, PAR-2 and PAR-3 mRNAs, but enhanced only PAR-1 protein expression. At 1 ng/ml, RANTES can abolish tryptase induced IL-13 release, but enhance trypsin, tryptase and thrombin induced PAR-1, -2 and -4 expression. LY204002 abolished RANTES induced IL-13 release, indicating an Akt cell signaling pathway may be involved in the event. In conclusion, RANTES can stimulate IL-13 release from mast cells through a CCR5 and Akt cell signaling pathway dependent mechanism. It can also enhance trypsin, tryptase and thrombin-induced expression of PARs in mast cells. RANTES may contribute to modulation of IL-13 production and PAR expression in mast cells, through which participates in the mast cell related inflammation.

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    • "Furthermore, tryptase-induced PAR-2 expression can be enhanced by IL-12 [20], TNF [31], RANTES [32], and IL-29 [29], and tryptase-induced PAR-3 and PAR-4 expression is upregulated by TNF on P815 mast cells [31]. It is also observed that trypsin-induced expression of PAR-1, -2, and -4 can be enhanced by RANTES [32] (Table 1). "
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