title: Mechanisms of murine lacrimal gland repair after experimentally induced inflammation.
abstract: OBJECTIVE
  The authors recently reported that a severe inflammatory response resulting in substantial loss of acinar cells was induced by a single injection of interleukin-1alpha into the lacrimal gland and that this effect was reversible. The purpose of the present study was to determine the mechanisms involved in lacrimal gland injury and repair.
  
  
  METHODS
  Inflammation was induced by direct injection of recombinant human interleukin-1alpha (IL-1alpha, 1 microg in 2 microL) into the exorbital lacrimal glands of anesthetized female BALB/c mice. Animals were killed 1, 2, 3, 4, 5, 6, or 7 days after injection. Exorbital lacrimal glands were then removed and processed for measurement of protein secretion, histology, immunohistochemistry, and Western blotting.
  
  
  RESULTS
  The results show that lacrimal gland acinar cells are lost through programmed cell death (apoptosis) and autophagy. They also show that the number of nestin (a stem cell marker)-positive cells increased 2 to 3 days after injury and that some of these cells were also positive for Ki67 (a cell proliferation marker) and alpha-smooth muscle actin (a marker of myoepithelial cells). Finally, they show that the amount of phosphorylated Smad1/5/8 (effector molecules of bone morphogenetic protein 7 [BMP7]) increased 2 to 3 days after injury and could also be detected in nestin-positive cells.
  
  
  CONCLUSIONS
  The lacrimal gland contains stem/progenitor cells capable of tissue repair after injury. Programmed cell death after injury triggers proliferation and differentiation of these cells, presumably through activation of the BMP7 pathway.
authors.affiliation: Department of General Dentistry, Tufts University School of Dental Medicine, Boston, Massachusetts 0211 , USA. driss.zoukhri@tufts.edu
authors.forename: Driss
authors.initials: D
authors.lastname: Zoukhri
authors.forename: Amanda
authors.initials: A
authors.lastname: Fix
authors.forename: Joseph
authors.initials: J
authors.lastname: Alroy
authors.forename: Claire L
authors.initials: CL
authors.lastname: Kublin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D003607:Dacryocystitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D053582:Interleukin-1alpha / Q000494:pharmacology; D007381:Intermediate Filament Proteins / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D007765:Lacrimal Apparatus / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D011994:Recombinant Proteins / Q000494:pharmacology; D051898:Smad1 Protein / Q000378:metabolism; D051902:Smad5 Protein / Q000378:metabolism; D051904:Smad8 Protein / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology; D014945:Wound Healing / Q000502:physiology*; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D053582:Interleukin-1alpha; D007381:Intermediate Filament Proteins; D019394:Ki-67 Antigen; D051907:Lysosomal Membrane Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D064231:Nestin; D011994:Recombinant Proteins; D051898:Smad1 Protein; D051902:Smad5 Protein; D051904:Smad8 Protein; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1; C480860:Map1lc3b protein, mouse; C577484:NES protein, human; C577485:Nes protein, mouse; C497401:Smad1 protein, mouse; C497798:Smad5 protein, mouse; C491621:Smad9 protein, mouse