HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: iovs.08-1730v1 49/10/4399    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Zoukhri, D. Articles by Kublin, C. L. PubMed PubMed Citation Articles by Zoukhri, D. Articles by Kublin, C. L.

Mechanisms of Murine Lacrimal Gland Repair after Experimentally Induced Inflammation

¹From the Department of General Dentistry, Tufts University School of Dental Medicine, Boston, Massachusetts; the ²Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts; and the ³Department of Pathology, Tufts University School of Medicine, Cummings School of Veterinary Medicine and Tufts-New England Medical Center, Boston, Massachusetts.

PURPOSE. The authors recently reported that a severe inflammatory response resulting in substantial loss of acinar cells was induced by a single injection of interleukin-1 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-1 (IL-1, 1 µg in 2 µL) 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 -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.