title: The TGF-β co-receptor endoglin regulates macrophage infiltration and cytokine production in the irradiated mouse kidney.
abstract: OBJECTIVE
  We previously showed that mice with reduced levels of the transforming growth factor-beta (TGF-β) co-receptor endoglin (Eng(+/-) mice) develop less fibrosis and vascular damage after kidney irradiation than their wild type (Eng(+/+) mice) littermates; however, the underlying mechanism was unclear. Results from current studies suggest that this occurs via modulation of the radiation-induced inflammatory response.
  
  
  METHODS
  Kidneys of Eng(+/+) and Eng(+/-) mice were irradiated with 16Gy. Mice were sacrificed at 20weeks after irradiation and gene expression and protein levels were analyzed.
  
  
  RESULTS
  Kidney irradiation triggered the infiltration of macrophages in both Eng(+/+) and Eng(+/-) mice, however, levels of macrophage-produced cytokines interleukin 1 beta (Il1b) and interleukin 6 (Il6) were reduced in irradiated Eng(+/-) compared to Eng(+/+) mice. Double immuno-stainings confirmed that IL-6 was produced by macrophages, whereas IL-1β was mainly detected in other cell types. Accordingly, inflammatory cell precursors derived from the bone marrow of Eng(+/-) mice showed impaired ability to express Il1b and Il6 compared to wild type mice.
  
  
  CONCLUSIONS
  Endoglin promotes kidney inflammation after irradiation by regulating macrophage infiltration and interleukin production, thereby promoting pathogenic changes after radiation exposure.
authors.affiliation: Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam, The Netherlands. m.scharpfenecker@nki.nl
authors.forename: Marion
authors.initials: M
authors.lastname: Scharpfenecker
authors.forename: Ben
authors.initials: B
authors.lastname: Floot
authors.forename: Nicola S
authors.initials: NS
authors.lastname: Russell
authors.forename: Fiona A
authors.initials: FA
authors.lastname: Stewart
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D000071063:Endoglin; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000473:pathology / Q000528:radiation effects*; D008264:Macrophages / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011833:Radiation Injuries, Experimental; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism
chemical_list: D016207:Cytokines; D000071063:Endoglin; C502004:Eng protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D018125:Receptors, Transforming Growth Factor beta