It has been reported that
HMGB1 participated in various types of
lung injury. In this study, we explored whether blocking
HMGB1 has a preventive effect on the early radiation-induced
lung injury and investigate the mechanism. Mice model of radiation-induced
lung injury were accomplished by a single dose irradiation (15 Gy) to the whole thorax. Irradiated mice were treated with HMGB1-neutralizing antibody intraperitoneally dosed 10 μg, 50 μg, 100 μg/mouse respectively and were sacrificed after one week post-irradiation. Lung tissue slices were stained by H&E, and alveolitis was quantified by Szapiel scoring system. The level of
cytokines TNF-γ in bronchoalveolar lavage fluid was detected by ELISA method. And p65NF-κB, p50NF-κB
protein expression in mice lung tissues was detected by Western blot analysis. The results showed that blocking
HMGB1 inhibited the inflammatory response, and thereby decreased the degree of alveolitis of irradiated lung tissue. In addition,
HMGB1 antagonist can restrain the expression of type Th2 or Th17 derived inflammatory
cytokines TNF-α,
IL-6 and
IL-17A, promote the expression of Th1 type
cytokines INF-γ, and inhibit p65 NF-κB but promote p50 NF-κB activation, which promoted the resolution of the radiation-induced inflammatory response. In conclusion, blocking
HMGB1 can reduce the degree of early radiation-induced
lung injury, and its mechanism may be related to the promotion of p50NF-κB activation and its downstream molecules expression. Inhibiting
HMGB1 may be a new target to deal with early radiation-induced
lung injury.