HSP27 inhibitor attenuates radiation-induced pulmonary inflammation

Abstract

Radiation therapy has been used to treat over 70% of thoracic cancer; however, the method usually causes radiation pneumonitis. In the current study, we investigated the radioprotective effects of HSP27 inhibitor (J2) on radiation-induced lung inflammation in comparison to amifostine. In gross and histological findings, J2 treatment significantly inhibited immune cell infiltration in lung tissue, revealing anti-inflammatory potential of J2. Normal lung volume, evaluated by micro-CT analysis, in J2-treated mice was higher compared to that in irradiated mice. J2-treated mice reversed radiation-induced respiratory distress. However, amifostine did not show significant radioprotective effects in comparison to that of J2. In HSP27 transgenic mice, we observed increased immune cells recruitment and decreased volume of normal lung compared to wild type mice. Increased ROS production and oxidative stress after IR were down-regulated by J2 treatment, demonstrating antioxidant property of J2. The entire data of this study collectively showed that J2 may be an effective therapeutic agent for radiation-induced lung injury.

LXA4-FPR2 signaling regulates radiation-induced pulmonary fibrosis via crosstalk with TGF-β/Smad signaling

“…To mimic the effects of clinical radiotherapy in an animal model of IR-induced lung damage, we had previously exposed mice lungs to high-dose radiation using a small-animal micro-irradiator (X-RAD320) equipped with a collimator system (to produce focal radiation beams) 7,8,28 . These studies showed that radiation pneumonitis occurs in mice within 2 weeks of exposure to 60-100 Gy of IR 8,15,28 . Herein, we evaluated the effects of LXA 4 on pneumonitis 2 weeks after 75 Gy IR by evaluating the lung morphology and performing hematoxylin and eosin (H&E) staining and pulmonary function assays (micro-computed tomography (CT) and flexiVent TM ).…”

“…1c). Microcomputed tomographic (micro-CT) images taken 2 weeks after IR show that pulmonary consolidation throughout the left lung of irradiated mice makes it possible to measure high air-tissue contrast 8,28 . We found that LXA 4 reduced IR-induced pulmonary consolidation ( Fig.…”

“…Modern clinical radiotherapy techniques, including stereotactic radiotherapy (SBRT)-which delivers small fractions of ablative radiation doses-are more accurate and precise than conventional radiotherapy techniques. Previously, we had developed a mouse model that simulates SBRT; we used an image-guided smallanimal IR system to deliver a single high dose of radiation to the lung and verified the induction of pulmonary fibrosis in response to IR [6][7][8] .…”

MAPKAPK2 (MK2) inhibition mediates radiation-induced inflammatory cytokine production and tumor growth in head and neck squamous cell carcinoma

“…HSP27 can also mediate the effects of certain therapeutic approaches. RT increased levels of HSP27 and p-HSP27 in head and neck cancer cell lines [28], and in mouse lung in vivo [29]. Pavan and colleagues [30] found that HSP27 was required for spontaneous lung metastasis in a mouse model of ovarian cancer and inhibition of HSP27 has been shown to sensitize tumors to chemotherapy [30] and RT [31].…”

PM014 attenuates radiation-induced pulmonary fibrosis via regulating NF-kB and TGF-b1/NOX4 pathways

“…Quantification was performed by comparative CT method (∆∆CT). Extracted 30 μg proteins were separated by SDS-PAGE, the membranes were probed with primary antibody (1:1000), followed by incubation with horseradish peroxidase-coupled secondary antibody 45 . Detection was performed with a chemiluminescence-based detection kit (Bio-Rad, Hercules, CA, USA).…”