Table 2 Studies analyzing the effects of specific defects in danger signaling/immune regulation after whole thorax irradiation or Bleomycin treatment
From: Modeling DNA damage-induced pneumopathy in mice: insight from danger signaling cascades
Strain | Whole thorax irradiation | Ref. | Bleomycin | Ref. |
|---|---|---|---|---|
TLR2−/− | - 18Gy, endpoint 26wks - pneumonitis and fibrosis development like WT | Paun | - intratracheal, 2 U/kg, endpoint 21d - reduced BALF cells - enhanced BALF IL-17 level - reduced BALF TGF-b and IL-27 - reduced fibrosis development | Kim |
- intratracheal, 3 U/kg, endpoint 28d - reduced M1/M2, Treg and pDC - reduced HMGB1 and TGF-β - reduced apoptosis of pulmonary cells - reduced fibrosis developemnt | Yang | |||
TLR4−/− | - 18Gy, endpoint 26wks - pneumonitis and fibrosis development like WT | Paun | - intratracheal, 3 U/kg, endpoint 28d - enhanced inflammatory cells - enhanced immunosuppressive cytokines - attenuation of pro-infl. p38 signaling - activation of immunosuppressive ERK signaling - enhanced fibrosis developemnt | Yang |
TLR2/4−/− | - 18Gy, endpoint 26wks - same infiltration compared to WT - same apoptosis induction like WT - enhanced fibrosis development | Paun | - intratracheal, 5 U/kg, endpoint 21d - reduced survival - reduced BAL cells and PMN - enhanced apoptotic cells - enhanced inflammation | Jiang |
MyD88−/− | - 14Gy, endpoint 27wks - enhanced TH2 cells - enhanced fibrosis development | Brickey | - intratracheal, 5 U/kg, endpoint 21d - reduced BAL cells and PMN - enhanced apoptotic cells - enhanced inflammation | Jiang |
- nasal, 15 U/kg, endpoint 21 d - reduced lymphocytes, neutrophils, macrophages - reduced pro-infl. cytokines - reduced TGF-β, TIMP-1 and MMP2/9 - reduced inflammation and fibrosis | Gasse | |||
CD73−/− | - 15Gy, endpoint 25-30wks - reduced adenosine in BALF - reduced early apoptosis - reduced pro-fibrotic factors - reduced fibrosis development | Wirsdorfer | - intratracheal, 3.5 U/kg, endpoint 14d - reduced adenosine in BALF - enhanced lymphocytes, neutrophils, macrophages - enhanced pro-infl. and pro-fibr. factors - enhanced collagen and fibrosis | Volmer |
IL-6−/− | - 10Gy, endpoint 4wks - stable CD44 and Bak level compared to WT (enhanced) - same inflammatory foci induction compared to WT | Sakai | - intratracheal, 1 U/kg, endpoint 21d - reduced acute neutrophil infiltration (d2) - reduced BAL cell counts (d2, d21) - reduced collagen and fibrosis | Saito |
- C-lon 10Gy, endpoint 24wks - same macrophage infiltration at week 12, 24 - reduced fibrosis development | Saito-Fujita | |||
IL-4−/− | - 12.5 Gy, endpoint 26wks - reduced M2 macrophages - fibrosis development like WT | Groves | - intratracheal, 1 U/kg (2.5 U/kg), endpoint 28d - 100% mortality at d12, 2.5 U/kg treated mice - reduced eosinophils, neutrophils, macrophages at d7 - reduced lymphocytes at d14 - reduced collagen, fibronectin, fibrosis at d28 | Huaux |
- intratracheal, 2.2 U/kg, endpoint 14d - same BAL cell level compared to WT - enhanced z score values for hydroxyproline, fibrosis fraction | Izbicki | |||
SCID mice - intratracheal, 3 U/kg, endpoint 21d - fibrosis development like WT | Lake-Bullock | |||
RAG2−/−, athymic NudeSCID | RAG2−/− mice | Cappuccini | athymic Nude mice -intratracheal, 3 U/kg, endpoint 14d - reduced lung collagen synthesis compared to WT | Schrier |
- 15Gy, endpoint 24wks - prominent fibrosis already in week 24 p.l. | athymic Nude mice "low" dose intraperitoneal 8 times - 20 U/kg 2 times/week, endpoint 8wks - mild alveolitis and fibrosis athymic Nude mice "medium" dose intraperitoneal 8 times - 50 U/kg, 4 times/week, endpoint 4wks- prominent alveolitis and fibrosis | Szapiel |