Interleukin-1α-dependent Regulation of Matrix Metalloproteinase-9 (MMP-9) Secretion and Activation in the Epithelial Cells of Odontogenic Jaw Cysts

Abstract

Interleukin-la (IL-1α) and matrix metalloproteinase-9 (MMP-9) are thought to be involved in odontogenic cyst expansion. In this study, we investigated the effects of IL-1α 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-1α 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-1α (rhIL-la) 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-la and proMMP-9 without stimulation. Under the cultivation on a fibronectin-coated dish, rhIL-la increased the secretion of proMMP-9 from the epithelial cells in a dose-dependent manner. Moreover, rhIL-la 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-la and plasminogen. Hence, our results suggest that IL-1α 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.

Keywords

odontogenic jaw cysts interleukin-1α (IL-1α)matrix metalloproteinase-9 (MMP-9).

Get full access to this article

View all access options for this article.

References

Allan JA , Docherty AJ , Barker PJ , Huskisson NS , Reynolds JJ , Murphy G. (1995). Binding of gelatinases A and B to type-I collagen and other matrix components. Biochem J 309:299-306.

Arner EC , Tortorella MD (1995). Signal transduction through chondrocyte integrin receptors induces matrix metalloproteinase synthesis and synergizes with interleukin-1 . Arthritis Rheum 38:1304-1314.

Davies B. , Waxman J. , Wasan H. , Abel P. , Williams G. , Krausz T. , et al. (1993). Levels of matrix metalloproteases in bladder cancer correlate with tumor grade and invasion. Cancer Res 53:5365-5369.

Dayer JM , de Rochemonteix B. , Burrus B. , Demczuk S. , Dinarello CA (1986). Human recombinant interleukin 1 stimulates collagenase and prostaglandin E2 production by human synovial cells. J Clin Invest 77:645-648.

Donoff RB , Harper E. , Guralnick WC (1972). Collagenolytic activity in keratocysts. J Oral Surg 30:879-884.

Dinarello CA (1989). Interleukin-1 and its biologically related cytokines . Adv Immunol 44:153-205.

Esteve PO , Tremblay P. , Houde M. , St-Pierre Y. , Mandeville R. (1998). In vitro expression of MMP-2 and MMP-9 in glioma cells following exposure to inflammatory mediators. Biochim Biophys Acta 1403:85-96.

Formigli L. , Orlandini SZ , Tonelli P. , Giannelli M. , Martini M. , Brandi ML , et al. (1995). Osteolytic processes in human radicular cysts: morphological and biochemical results. J Oral Pathol Med 24:216-220.

Gao Z. , Mackenzie IC , Cruchley AT , Williams DM , Leigh I. , Lane EB ( 1989). Cytokeratin expression of the odontogenic epithelia in dental follicles and developmental cysts. J Oral Pathol Med 18:63-67.

10.

Gowen M. , Wood DD , Ihrie EJ , McGuire MK , Russell RG (1983). An interleukin 1-like factor stimulates bone resorption in vitro. Nature 306:378-380.

11.

He CS , Wilhelm SM , Pentland AP , Marmer BL , Grant GA , Eisen AZ , et al. (1989). Tissue cooperation in a proteolytic cascade activating human interstitial collagenase. Proc Natl Acad Sci USA 86:2632-2636.

12.

Heussen C. , Dowdle EB (1980). Electrophoretic analysis of plasminogen activators in polyacrylamide gels containing sodium dodecyl sulfate and copolymerized substrates. Anal Biochem 102:196-202.

13.

Hormia M. , Ylipaavalniemi P. , Nagle RB , Virtanen I. (1987). Expression of cytokeratins in odontogenic jaw cysts: monoclonal antibodies reveal distinct variation between different cyst types. J Oral Pathol 16:338-346.

14.

Kinoh H. , Sato H. , Tsunezuka Y. , Takino T. , Kawashima A. , Okada Y. , et al. (1996). MT-MMP, the cell surface activator of proMMP-2 (progelatinase A), is expressed with its substrate in mouse tissue during embriogenesis. J Cell Sci 109:953-959.

15.

Meghji S. , Henderson B. , Bando Y. , Harris M. (1992). Interleukin-1 : the principal osteolytic cytokine produced by keratocysts. Arch Oral Biol 37:935-943.

16.

Moll R. , Franke WW , Schiller DL , Geiger B. , Krepler R. (1982). The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell 31:11-24.

17.

O'Grady RL , Nethery A. , Hunter N. (1984). A fluorescent screening assay for collagenase using collagen labeled with 2-methoxy-2,4-diphenyl-3(2H)-furanone. Anal Biochem 140:490-494.

18.

Ogata Y. , Enghild JJ , Nagase H. (1992). Matrix metalloproteinase 3 (stromelysin) activates the precursor for the human matrix metalloproteinase 9. J Biol Chem 267:3581-3584.

19.

Okada Y. , Gonoji Y. , Naka K. , Tomita K. , Nakanishi I. , Iwata K. , et al. (1992). Matrix metalloproteinase 9 (92-kDa gelatinase/type IV collagenase) from HT 1080 human fibrosarcoma cells. Purification and activation of the precursor and enzymic properties. J Biol Chem 267:21712-21719.

20.

Ratkay LG , Waterfield JD , Tonzetich J. (1995). Stimulation of enzyme and cytokine production by methyl mercaptan in human gingival fibroblast and monocyte cell cultures . Arch Oral Biol 40:337-344.

21.

Richards D. , Rutherford RB (1990). Interleukin-1 regulation of procollagenase mRNA and protein in periodontal fibroblasts in vitro. J Periodont Res 25:222-229.

22.

Saito S. , Ngan P. , Rosol T. , Saito M. , Shimizu H. , Shinjo N. , et al. (1991). Involvement of PGE synthesis in the effect of intermittent pressure and interleukin-1 β on bone resorption. J Dent Res 70:27-33.

23.

Salo T. , Lyons JG , Rahemtulla F. , Birkedal-Hansen H. , Larjava H. (1991). Transforming growth factor β1 up-regulates type IV collagenase expression in cultured human keratinocytes. J Biol Chem 266:11436-11441.

24.

Sato H. , Seiki M. (1993). Regulatory mechanism of 92 kDa type IV collagenase gene expression which is associated with invasiveness of tumor cells. Oncogene 8:395-405.

25.

Shapiro SD , Kobayashi DK , Pentland AP , Welgus HG (1993). Induction of macrophage metalloproteinases by extracellular matrix. Evidence for enzyme- and substrate-specific responses involving prostaglandin-dependent mechanisms. J Biol Chem 268:8170-8175.

26.

Sorsa T. , Ylipaavalniemi P. , Suomalainen K. , Vauhkonen M. , Lindy S. (1988). Type-specific degradation of interstitial collagens by human keratocyst capsule collagenase. Med Sci Res 16:1189-1190.

27.

Sorsa T. , Salo T. , Koivunen E. , Tyynela J. , Konttinen YT , Bergmann U. , et al. (1997). Activation of type IV procollagenases by human tumor-associated trypsin-2. J Biol Chem 272:21067-21074.

28.

Teronen 0 , Salo T. , Konttinen YT , Rifkin B. , Vemillo A. , Ramamurthy NS , et al. (1995a). Identification and characterization of gelatinases/type IV collagenases in jaw cysts. J Oral Pathol Med 24:78-84.

29.

Teronen 0 , Salo T. , Laitinen J. , Törnwall J. , Ylipaavalniemi P. , Konttinen YT , et al. (1995b). Characterization of interstitial collagenases in jaw cyst wall. Eur J Oral Sci 103:141-147.

30.

Tewari M. , Tuncay OC , Milchman A. , Reddy PJ , Reddy CD , Cressman DE , et al. (1996). Association of interleukin-1-induced, NFKB DNA-binding activity with collagenase gene expression in human gingival fibroblasts . Arch Oral Biol 41:461-468.