Department of Microbiology/Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Int J Radiat Biol. 2012 Apr;88(4):335-47. doi: 10.3109/09553002.2012.652723. Epub 2012 Feb 6.
The role of innate immune regulators is investigated in injury sustained from irradiation as in the clinic for cancer treatment or from a nuclear incident. The protective benefits of flagellin signaling through Toll-like receptors (TLR) in an irradiation setting warrant study of a key intracellular adaptor of TLR signaling, namely Myeloid differentiation primary response factor 88 (MyD88). The role of MyD88 in regulating innate immunity and Nuclear factor kappa-B (NF-κB)-activated responses targets this critical factor for influencing injury and recovery as well as maintaining immune homeostasis.
To examine the role of MyD88, we examined immune cells and factors during acute pneumonitic and fibrotic phases in Myd88-deficient animals receiving thoracic gamma (γ)-irradiation.
We found that MyD88 supports survival from radiation-induced injury through the regulation of inflammatory factors that aid in recovery from irradiation. The absence of MyD88 resulted in unresolved pulmonary infiltrate and enhanced collagen deposition plus elevated type 2 helper T cell (Th2) cytokines in long-term survivors of irradiation.
These results based only on a gene deletion model suggest that alterations of MyD88-dependent inflammatory processes impact chronic lung injury. Therefore, MyD88 may contribute to attenuating long-term radiation-induced lung injury and protecting against fibrosis.
研究固有免疫调节剂在因癌症治疗或核事故而受到辐射损伤中的作用。鞭毛蛋白通过 Toll 样受体（TLR）发出信号在辐射环境中具有保护作用，因此有必要研究 TLR 信号的一个关键细胞内衔接蛋白，即髓样分化初级反应因子 88（MyD88）。MyD88 在调节固有免疫和核因子 kappa-B（NF-κB）激活反应中的作用将这个关键因素作为影响损伤和恢复以及维持免疫稳态的靶点。
为了研究 MyD88 的作用，我们在接受胸部 γ 射线照射的 Myd88 缺陷动物中，检查了急性气肿性和纤维化阶段的免疫细胞和因子。
我们发现，MyD88 通过调节有助于从照射中恢复的炎症因子来支持辐射诱导损伤的存活。MyD88 的缺失导致放射性肺损伤未得到解决，胶原沉积增加，长期存活的照射动物中 2 型辅助 T 细胞（Th2）细胞因子水平升高。
这些仅基于基因缺失模型的结果表明，MyD88 依赖性炎症过程的改变会影响慢性肺损伤。因此，MyD88 可能有助于减轻长期放射性肺损伤并预防纤维化。
