HSP27 inhibitor J2 (J2) (J2) is a HSP27 inhibitor, inhibits a production of HSP27 giant polymers, thereby having an effect of inhibiting a chaperone function of the HSP27 and reducing a cell protection function.

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.J2 may be an effective therapeutic agent for radiation-induced lung injury[1].

Male C57BL/6 mice (age, 6 weeks; weight, 20–25 g), and were acclimatized (n = 5 per cage) for a week before irradiation. A single dose of 75 Gy was delivered to the left lung in a single fraction using image-guided small-animal irradiator (X-RAD 320) that was equipped with a collimator system composed of 3.5-cm-thick copper to produce focal radiation beams, as well as an imaging subsystem consisting of a fluorescent screen coupled to a charge-coupled-device camera. We selected 3-mm collimators to mimic clinical SBRT conditions by irradiating only a small volume of tissue. The mice were divided into six groups (n = 6–8 per group) as follows: (1) control (C);(2) irradiation (IR) - mice were exposed to a single dose of 75 Gy delivered to the left lung in a single fraction; (3) irradiation + J2 (IR + J2) ?15 mg/kg of J2 was intraperitoneal administered on every other day after irradiation;(4) irradiation + amifostine (IR + Ami) ?100 mg/kg of amifostine were intraperitoneal administered on every other day after irradiation; (5) J2 only (J2) ?15 mg/kg of J2 were intraperitoneal administered on every other day without irradiation; (6) Amifostine only (Ami) ?100 mg/kg of amifostine were intraperitoneal administered on every other day without irradiation. On day 14, mice were sacrificed by CO2 asphyxiation, and their lung tissues were collected for analysis[1].