Swiprosin‐1 is expressed in mast cells and up‐regulated through the protein kinase CβI/η pathway

Abstract

Swiprosin-1 exhibits the highest expression in CD8(+) T cells and immature B cells and has been thought to play a role in lymphocyte physiology. Here we report that swiprosin-1 is also expressed in mast cells and up-regulated in both in vitro cultured mast cells by phorbol ester and in vivo model tissues of passive cutaneous anaphylaxis and atopic dermatitis. Targeted inhibition of the specific protein kinase C (PKC) isotypes by siRNA revealed that PKC-beta I/eta are involved in the expression of swiprosin-1 in the human mast cell line HMC-1. In contrast, down-regulation of swiprosin-1 by A23187 or ionomycin suggests that calcium-signaling plays a negative role. The ectopic expression of swiprosin-1 augmented PMA/A23187-induced NF-kappaB promoter activity, and resulted in increased expression of cytokines. Moreover, knock-down of swiprosin-1 attenuated PMA/A23187-induced cytokine expression. Collectively, these results suggest that swiprosin-1 is a PKC-beta I/eta-inducible gene and it modulates mast cell activation through NF-kappaB-dependent pathway.