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Tat-CIAPIN1 protein prevents against cytokine-induced cytotoxicity in pancreatic RINm5F β-cells

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Cytokines activate inflammatory signals and are major mediatorsin progressive β-cell damage, which leads to type 1 diabetes mellitus. We recently showed that the cell-permeable Tat-CIAPIN1fusion protein inhibits neuronal cell death induced by oxidativestress. However, how the Tat-CIAPIN1 protein affects cytokine-induced β-cell damage has not been investigated yet. Thus, we assessed whether the Tat-CIAPIN1 protein can protectRINm5F β-cells against cytokine-induced cytotoxicity. In cytokineexposedRINm5F β-cells, the transduced Tat-CIAPIN1 proteinelevated cell survivals and reduced reactive oxygen species(ROS) and DNA fragmentation levels. The Tat-CIAPIN1 proteinreduced mitogen-activated protein kinases (MAPKs) and NF-κBactivation levels and elevated Bcl-2 protein, whereas Bax andcleaved Caspase-3 proteins were decreased by this fusion protein. Thus, the protection of RINm5F β-cells by the Tat-CIAPIN1protein against cytokine-induced cytotoxicity can suggest thatthe Tat-CIAPIN1 protein might be used as a therapeutic inhibitoragainst RINm5F β-cell damage.

Abstract

Cytokines activate inflammatory signals and are major mediatorsin progressive β-cell damage, which leads to type 1 diabetes mellitus. We recently showed that the cell-permeable Tat-CIAPIN1fusion protein inhibits neuronal cell death induced by oxidativestress. However, how the Tat-CIAPIN1 protein affects cytokine-induced β-cell damage has not been investigated yet. Thus, we assessed whether the Tat-CIAPIN1 protein can protectRINm5F β-cells against cytokine-induced cytotoxicity. In cytokineexposedRINm5F β-cells, the transduced Tat-CIAPIN1 proteinelevated cell survivals and reduced reactive oxygen species(ROS) and DNA fragmentation levels. The Tat-CIAPIN1 proteinreduced mitogen-activated protein kinases (MAPKs) and NF-κBactivation levels and elevated Bcl-2 protein, whereas Bax andcleaved Caspase-3 proteins were decreased by this fusion protein. Thus, the protection of RINm5F β-cells by the Tat-CIAPIN1protein against cytokine-induced cytotoxicity can suggest thatthe Tat-CIAPIN1 protein might be used as a therapeutic inhibitoragainst RINm5F β-cell damage.

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