MyD88 provides a protective role in long-term radiation-induced lung injury.

Published

Journal Article

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Full Text

Duke Authors

Cited Authors

  • Brickey, WJ; Neuringer, IP; Walton, W; Hua, X; Wang, EY; Jha, S; Sempowski, GD; Yang, X; Kirby, SL; Tilley, SL; Ting, JP-Y

Published Date

  • April 2012

Published In

Volume / Issue

  • 88 / 4

Start / End Page

  • 335 - 347

PubMed ID

  • 22248128

Pubmed Central ID

  • 22248128

Electronic International Standard Serial Number (EISSN)

  • 1362-3095

Digital Object Identifier (DOI)

  • 10.3109/09553002.2012.652723

Language

  • eng

Conference Location

  • England