Irradiation leads to apoptosis of Kupffer Cells by a HSP27- dependant pathway followed by release of TNF-alpha

In our previous publication we were able to show that irradiation of Kupffer cells, the liver resident macrophages, leads to an increased TNF-α- concentration in the culture medium. The pathomechanisms underlying this phenomenon however left to be elucidated.

Northern- Blot analysis revealed that TNF-α- gene expression of Kupffer- cells did not change due to irradiation indicating that changes of the TNF-α concentration in the culture medium is regulated on protein level. Following irradiation apoptosis rate increased drastically within 48h. Contemporarily total TNF-α concentration in cell lysates of Kupffer cells being attached to the culture plate decreased. However normalization of the TNF-α concentration on cell number revealed that TNF-α concentration per attached cell left constant during the period of observation. Using a rat array it revealed that HSP27 is strongly downregulated and bax is upregulated in irradiated Kupffer cells compared to the non irradiated controls. When compared to controls, overexpression of HSP27 in Kupffer cells followed by irradiation could prevent the effect of irradiation on bax- expression, apoptosis and contemporarily on increase of TNF-α concentration in the Kupffer cell medium.

Irradiation of Kupffer cells leads to apoptosis due to downregulation of HSP27 and consecutively to upregulation of bax- expression. Furthermore apoptosis of Kupffer cells leads to increase of TNF-α concentration in the culture medium which may be due cell death but not due to active release or synthesis.

Apoptosis; Irradiation; Kupffer-Cells; HSP27; TNF-alpha