Interleukin-1alpha-dependent regulation of matrix metalloproteinase-9(MMP-9) secretion and activation in the epithelial cells of odontogenic jaw cysts.
Interleukin-1alpha (IL-1alpha) and matrix metalloproteinase-9 (MMP-9) are thought to be involved in odontogenic cyst expansion. In this study, we investigated the effects of IL-1alpha on the secretion and activation of MMP-9 in odontogenic jaw cysts. An active form of MMP-9 was present in odontogenic keratocyst (6 of 8 cases) fluids more frequently than dentigerous cyst (3 of 10 cases) and radicular cyst (3 of 10 cases) fluids, although proMMP-9 was present in all cyst fluids. Odontogenic keratocyst fragments in explant culture secreted a larger amount of IL-1alpha than dentigerous cyst and radicular cyst fragments in explant culture, and spontaneously secreted both proMMP-9 and an active form of MMP-9. The fragments of dentigerous cysts and radicular cysts secreted a small amount of proMMP-9, but no active form of MMP-9. Exogenously added recombinant human IL-1alpha (rhlL-1alpha) increased the secretion and activation of proMMP-9 in the fragments of dentigerous cysts and radicular cysts. The epithelial cells isolated from odontogenic keratocysts secreted IL-1alpha and proMMP-9 without stimulation. Under the cultivation on a fibronectin-coated dish, rhIL-1alpha increased the secretion of proMMP-9 from the epithelial cells in a dose-dependent manner. Moreover, rhIL-1alpha induced the secretion of proMMP-3 and plasminogen activator urokinase (u-PA) from the epithelial cells, and converted the secreted proMMP-3 to the active form in the presence of plasminogen. The secreted proMMP-9 was also activated in the presence of rhIL-1alpha and plasminogen. Hence, our results suggest that IL-1alpha may up-regulate not only proMMP-9 secretion but also proMMP-9 activation by inducing proMMP-3 and u-PA production in the cyst epithelial cells by autocrine/paracrine regulatory mechanisms.
Kubota
Y
Y
Second Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Kyushu University, Fukuoka, Japan. yasu@dent.kyushu-u.ac.jp
Ninomiya
T
T
Oka
S
S
Takenoshita
Y
Y
Shirasuna
K
K
D019898:Autocrine Communication / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D020420:Cyst Fluid / Q000201:enzymology; D003803:Dentigerous Cyst / Q000201:enzymology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004792:Enzyme Precursors / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000201:enzymology; D005353:Fibronectins; D006801:Humans; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D019278:Matrix Metalloproteinase 3 / Q000187:drug effects / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects / Q000378:metabolism*; D009807:Odontogenic Cysts / Q000201:enzymology / Q000473:pathology*; D019899:Paracrine Communication / Q000187:drug effects; D010960:Plasminogen Activators / Q000187:drug effects / Q000378:metabolism; D011842:Radicular Cyst / Q000201:enzymology / Q000473:pathology; D011994:Recombinant Proteins; D015854:Up-Regulation / Q000187:drug effects; D014568:Urokinase-Type Plasminogen Activator / Q000187:drug effects / Q000378:metabolism
D003470:Culture Media; D004792:Enzyme Precursors; D005353:Fibronectins; D007375:Interleukin-1; D011994:Recombinant Proteins; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9