title: MyD88 provides a protective role in long-term radiation-induced lung injury.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Microbiology/Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Willie J
authors.initials: WJ
authors.lastname: Brickey
authors.forename: Isabel P
authors.initials: IP
authors.lastname: Neuringer
authors.forename: William
authors.initials: W
authors.lastname: Walton
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Hua
authors.forename: Ellis Y
authors.initials: EY
authors.lastname: Wang
authors.forename: Sushmita
authors.initials: S
authors.lastname: Jha
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Sempowski
authors.forename: Xuebin
authors.initials: X
authors.lastname: Yang
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Kirby
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Tilley
authors.forename: Jenny P-Y
authors.initials: JP
authors.lastname: Ting
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D055370:Lung Injury / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000378:metabolism*; D010994:Pleura / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D011658:Pulmonary Fibrosis / Q000150:complications / Q000378:metabolism / Q000517:prevention & control; D011833:Radiation Injuries, Experimental / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D053594:Myeloid Differentiation Factor 88; D003094:Collagen