Limits...
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.

Show MeSH

Related in: MedlinePlus

Effect of androgen deprivation including flutamide and castration on pro-inflammatory cytokines in lung, liver and intestinal tissues. (A-C) The mRNA levels of the cytokines TNF-α, IL-6, IL-1α/β and TGF-β were quantified by real-time RT-PCR. The results were normalized to the value of irradiated mice. The y-axis shows the RNA ratio of each target gene in lung (A), liver (B) and intestinal (C) tissue (control and irradiated mice with flutamide administration) divided by that in the irradiated mice (without flutamide administration). (D) Effect of flutamide on the MPO activities in lung, liver and intestinal tissues. The y-axis shows the ratio of MPO activity in irradiated tissues with flutamide administration or castration divided by irradiated tissues without androgen deprivation. Data are the mean ± SE. Columns, means of 3 separate experiments; bars, SD. * P < 0.05
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2667536&req=5

Figure 2: Effect of androgen deprivation including flutamide and castration on pro-inflammatory cytokines in lung, liver and intestinal tissues. (A-C) The mRNA levels of the cytokines TNF-α, IL-6, IL-1α/β and TGF-β were quantified by real-time RT-PCR. The results were normalized to the value of irradiated mice. The y-axis shows the RNA ratio of each target gene in lung (A), liver (B) and intestinal (C) tissue (control and irradiated mice with flutamide administration) divided by that in the irradiated mice (without flutamide administration). (D) Effect of flutamide on the MPO activities in lung, liver and intestinal tissues. The y-axis shows the ratio of MPO activity in irradiated tissues with flutamide administration or castration divided by irradiated tissues without androgen deprivation. Data are the mean ± SE. Columns, means of 3 separate experiments; bars, SD. * P < 0.05

Mentions: Real-time RT-PCR was used to quantify the expression of cytokines induced by radiation and their changes after androgen deprivation. First, low expression levels were noted in unirradiated control mice and there were no obvious changes after androgen deprivation (unirradiated F-mice and S-mice). Irradiation (20 Gy) induced a significant increase in the mRNA levels of detected cytokines of the experimental groups compared with the unirradiated group at 24 h. Castration augmented the increase in pro-inflammation cytokines in the irradiated lung, intestine, but not in liver (Figure 2A–C). However, our data demonstrated that androgen deprivation by flutamide did not induce obvious changes on RT-induced inflammation. In addition, a significant increase in MPO activity was observed in the irradiated lung and intestine after castration (Figure 2D). Administration of flutamide did not significantly affect the MPO activity in irradiated mice.


Androgen deprivation modulates the inflammatory response induced by irradiation.

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

Effect of androgen deprivation including flutamide and castration on pro-inflammatory cytokines in lung, liver and intestinal tissues. (A-C) The mRNA levels of the cytokines TNF-α, IL-6, IL-1α/β and TGF-β were quantified by real-time RT-PCR. The results were normalized to the value of irradiated mice. The y-axis shows the RNA ratio of each target gene in lung (A), liver (B) and intestinal (C) tissue (control and irradiated mice with flutamide administration) divided by that in the irradiated mice (without flutamide administration). (D) Effect of flutamide on the MPO activities in lung, liver and intestinal tissues. The y-axis shows the ratio of MPO activity in irradiated tissues with flutamide administration or castration divided by irradiated tissues without androgen deprivation. Data are the mean ± SE. Columns, means of 3 separate experiments; bars, SD. * P < 0.05
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Effect of androgen deprivation including flutamide and castration on pro-inflammatory cytokines in lung, liver and intestinal tissues. (A-C) The mRNA levels of the cytokines TNF-α, IL-6, IL-1α/β and TGF-β were quantified by real-time RT-PCR. The results were normalized to the value of irradiated mice. The y-axis shows the RNA ratio of each target gene in lung (A), liver (B) and intestinal (C) tissue (control and irradiated mice with flutamide administration) divided by that in the irradiated mice (without flutamide administration). (D) Effect of flutamide on the MPO activities in lung, liver and intestinal tissues. The y-axis shows the ratio of MPO activity in irradiated tissues with flutamide administration or castration divided by irradiated tissues without androgen deprivation. Data are the mean ± SE. Columns, means of 3 separate experiments; bars, SD. * P < 0.05
Mentions: Real-time RT-PCR was used to quantify the expression of cytokines induced by radiation and their changes after androgen deprivation. First, low expression levels were noted in unirradiated control mice and there were no obvious changes after androgen deprivation (unirradiated F-mice and S-mice). Irradiation (20 Gy) induced a significant increase in the mRNA levels of detected cytokines of the experimental groups compared with the unirradiated group at 24 h. Castration augmented the increase in pro-inflammation cytokines in the irradiated lung, intestine, but not in liver (Figure 2A–C). However, our data demonstrated that androgen deprivation by flutamide did not induce obvious changes on RT-induced inflammation. In addition, a significant increase in MPO activity was observed in the irradiated lung and intestine after castration (Figure 2D). Administration of flutamide did not significantly affect the MPO activity in irradiated mice.

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