Regulation and gene expression of chemokines and adhesion molecules in rat liver after gamma-irradiation

Radiation Induced Liver Diseases (RILD) is a serious clinical complication. CXC and CC chemokines are known to attract inflammatory cells and adhesion molecules play a role in transmigration process to the site of inflammation. Aim of study was to investigate gene expression of CXC, CC-chemokines and their receptor in relation to two adhesion molecules in rat liver after single dose gamma-irradiation. Macrophage inflammatory protein-2 (MIP-2) concentration in serum was measured by ELISA after exposing the rat liver to gamma-irradiation (25Gy). Livers of irradiated animals and of controls (sham-irradiated) were investigated at 1, 3, 6, 12, 24, and 48h after liver irradiation. Cryostat sections were used to detect inflammatory cells by immunohistochemistry and total RNA was extracted. Hepatocytes and kupffer cells primary cultures were irradiated. Increased numbers of neutrophil granulocytes attached to wall of the portal vessels (max. at 3–6h) were observed after single-dose of gamma-irradiation. Number of ED-1 (mononuclear phagocytes) positive cells were not increased at any time points after irradiation. Moncyte chemoattractant protein -1 (MCP-1) was increasingly detected in the wall of the portal vessels.In CXC chemokines, MIP-2 serum concentration was significantly increased up to (774±80 pg/ml) 3h after irradiation as compared to sham-irradiated controls. A statistically significant induction of MIP-2, CXCL-1, LIX and MCP-3 (CC-chemokine) in RNA was also observed at 1h with peak at 3h and followed by a continuous decrease thereafter. CXCR-2 receptor gene expression was also early up-regulated (1–48h) and a quick (1–3h) induction of ICAM-1 but no significant change of PECAM-1 was observed after rat liver irradiation. Irradiation also up-regulated MIP-2 mRNA and CXCR-2 in isolated hepatocytes (8Gy) and kupffer cell (8Gy). Single dose (unfractionated) gamma- irradiation administrated to the liver induces a transient accumulation of granulocytes within the portal area. Although, gamma-irradiation is able to induce significant increase of gene expression of chemokines, known to be involved also in recruitment of mono-nuclear phagocytes, no increase of these cells at any time point was observed. This may influence repair process.