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Androgen deprivation modulates the inflammatory response induced by irradiation.

Wu CT, Chen WC, Lin PY, Liao SK, Chen MF - BMC Cancer (2009)

Bottom Line: We found androgen deprivation by castration significantly augmented RT-induced inflammation, associated with the increase NF-kappaB activation and COX-2 expression.However, administration of flutamide had no obvious effect on the radiation-induced inflammation response in the lung and intestine.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Urology, Chang Gung Memorial Hospital, Linko, Taiwan. chuntewu@adm.cgmh.org.tw

ABSTRACT

Background: The aim of this study was to determine whether radiation (RT)-induced inflammatory responses and organ damage might be modulated by androgen deprivation therapies.

Methods: 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-beta1 and p-AKT to elucidate the related pathway responsible to irradiation (RT) -induced fibrosis.

Results: We found androgen deprivation by castration significantly augmented RT-induced inflammation, associated with the increase NF-kappaB 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-kappaB activation and COX-2 expression by castration or lupron treatment. In addition, our data suggest that TGF-beta1 and the induced epithelial-mesenchymal transition (EMT) via the PI3K/Akt signaling pathway may contribute to RT-induced fibrosis.

Conclusion: 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.

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Related in: MedlinePlus

Effects of flutamide administration and castration on the radiation- induced inflammation. Lung and intestinal tissue sections were subjected to histologic analyses using H&E staining (Magnification ×200) were performed on lung (A) and intestinal (B) sections. Three mice from each group were examined. Representative slides are shown for (a) unirradiated control mice, (b) irradiated mice at 24 h after 20 Gy irradiation, (c) flutamide-treated mice 24 h after 20 Gy irradiation and (d) castrated mice 24 h after 20 Gy irradiation. Increased acute inflammatory infiltrate was observed in the interstitium was detected 24 h after irradiation. Duplicate experiments were performed for the analysis.
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Figure 3: Effects of flutamide administration and castration on the radiation- induced inflammation. Lung and intestinal tissue sections were subjected to histologic analyses using H&E staining (Magnification ×200) were performed on lung (A) and intestinal (B) sections. Three mice from each group were examined. Representative slides are shown for (a) unirradiated control mice, (b) irradiated mice at 24 h after 20 Gy irradiation, (c) flutamide-treated mice 24 h after 20 Gy irradiation and (d) castrated mice 24 h after 20 Gy irradiation. Increased acute inflammatory infiltrate was observed in the interstitium was detected 24 h after irradiation. Duplicate experiments were performed for the analysis.

Mentions: No significant lesions were observed in non-irradiated tissues from mice of each group. Increased levels of acute inflammatory infiltrate were observed microscopically in the interstitium of the lung and intestine 24 h after exposure to 20 Gy. Flutamide administration resulted in a similar acute inflammatory response to those noted in irradiated mice (Figure 3A &3B). More pronounced RT- induced inflammation was noted in irradiated S-mice by microscopic examination. Because TGF-β1 reportedly is an important biologic marker to predict RT-induced fibrosis [20], we further examined TGF-β1 activity by immunochemical analysis under various conditions. As shown in Figure 4, very low TGF-β1 immunoreactivities were observed in the unirradiated lung and intestinal tissues for each group. Twenty-four hours after exposure to 20 Gy, a pronounced increase in TGF-β1 immunoreactivity was observed in these tissues. A combination of irradiation with androgen deprivation by castration or Lupron Depot resulted in an increase in TGF-β1 immunoreactivity compared to radiation treatment alone, demonstrated by immunochemical staining and Western blotting (Figure 4B &4C). On the other hand, flutamide administration didn't result in the induction of increased RT-induced inflammation.


Androgen deprivation modulates the inflammatory response induced by irradiation.

Wu CT, Chen WC, Lin PY, Liao SK, Chen MF - BMC Cancer (2009)

Effects of flutamide administration and castration on the radiation- induced inflammation. Lung and intestinal tissue sections were subjected to histologic analyses using H&E staining (Magnification ×200) were performed on lung (A) and intestinal (B) sections. Three mice from each group were examined. Representative slides are shown for (a) unirradiated control mice, (b) irradiated mice at 24 h after 20 Gy irradiation, (c) flutamide-treated mice 24 h after 20 Gy irradiation and (d) castrated mice 24 h after 20 Gy irradiation. Increased acute inflammatory infiltrate was observed in the interstitium was detected 24 h after irradiation. Duplicate experiments were performed for the analysis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2667536&req=5

Figure 3: Effects of flutamide administration and castration on the radiation- induced inflammation. Lung and intestinal tissue sections were subjected to histologic analyses using H&E staining (Magnification ×200) were performed on lung (A) and intestinal (B) sections. Three mice from each group were examined. Representative slides are shown for (a) unirradiated control mice, (b) irradiated mice at 24 h after 20 Gy irradiation, (c) flutamide-treated mice 24 h after 20 Gy irradiation and (d) castrated mice 24 h after 20 Gy irradiation. Increased acute inflammatory infiltrate was observed in the interstitium was detected 24 h after irradiation. Duplicate experiments were performed for the analysis.
Mentions: No significant lesions were observed in non-irradiated tissues from mice of each group. Increased levels of acute inflammatory infiltrate were observed microscopically in the interstitium of the lung and intestine 24 h after exposure to 20 Gy. Flutamide administration resulted in a similar acute inflammatory response to those noted in irradiated mice (Figure 3A &3B). More pronounced RT- induced inflammation was noted in irradiated S-mice by microscopic examination. Because TGF-β1 reportedly is an important biologic marker to predict RT-induced fibrosis [20], we further examined TGF-β1 activity by immunochemical analysis under various conditions. As shown in Figure 4, very low TGF-β1 immunoreactivities were observed in the unirradiated lung and intestinal tissues for each group. Twenty-four hours after exposure to 20 Gy, a pronounced increase in TGF-β1 immunoreactivity was observed in these tissues. A combination of irradiation with androgen deprivation by castration or Lupron Depot resulted in an increase in TGF-β1 immunoreactivity compared to radiation treatment alone, demonstrated by immunochemical staining and Western blotting (Figure 4B &4C). On the other hand, flutamide administration didn't result in the induction of increased RT-induced inflammation.

Bottom Line: We found androgen deprivation by castration significantly augmented RT-induced inflammation, associated with the increase NF-kappaB activation and COX-2 expression.However, administration of flutamide had no obvious effect on the radiation-induced inflammation response in the lung and intestine.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Urology, Chang Gung Memorial Hospital, Linko, Taiwan. chuntewu@adm.cgmh.org.tw

ABSTRACT

Background: The aim of this study was to determine whether radiation (RT)-induced inflammatory responses and organ damage might be modulated by androgen deprivation therapies.

Methods: 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-beta1 and p-AKT to elucidate the related pathway responsible to irradiation (RT) -induced fibrosis.

Results: We found androgen deprivation by castration significantly augmented RT-induced inflammation, associated with the increase NF-kappaB 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-kappaB activation and COX-2 expression by castration or lupron treatment. In addition, our data suggest that TGF-beta1 and the induced epithelial-mesenchymal transition (EMT) via the PI3K/Akt signaling pathway may contribute to RT-induced fibrosis.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus