Androgen deprivation modulates the inflammatory response induced by irradiation

The mRNA and tissue sections obtained from the lungs, intestines and livers of irradiated mice with or without androgen deprivation were analyzed by real-time PCR and histological analysis. Activation of NF-kappa B was examined by measuring nuclear protein levels in the intestine and lung 24 h after irradiation. We also examined the levels of cyclooxygenase-2 (COX-2), TGF-β1 and p-AKT to elucidate the related pathway responsible to irradiation (RT) -induced fibrosis.We found androgen deprivation by castration significantly augmented RT-induced inflammation, associated with the increase NF-κB activation and COX-2 expression. However, administration of flutamide had no obvious effect on the radiation-induced inflammation response in the lung and intestine. These different responses were probably due to the increase of RT-induced NF-κB activation and COX-2 expression by castration or lupron treatment. In addition, our data suggest that TGF-β1 and the induced epithelial-mesenchymal transition (EMT) via the PI3K/Akt signaling pathway may contribute to RT-induced fibrosis.When irradiation was given to patients with total androgen deprivation, the augmenting effects on the RT-induced inflammation and fibrosis should take into consideration for complications associated with radiotherapy.Although radiotherapy is an important cancer treatment modality, the cell killing induced by radiation is not tumor- or cell-type specific. Treatment of cancer patients with radiation can be significantly compromised by the development of severe acute and late damage to normal tissues. Normal tissue complications induced by irradiation differ depending on the target organ and cell types. Sequelae of pelvic RT include small bowel obstruction, enteritis, proctitis and radiation cystitis [1,2], and the lung is one of the most critical dose- limiting organs after thoracic RT. Recent studies have led towards a better understanding of the molecular mechanisms underlying radiation injury [3-5]. The