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Gene Review

MMP8  -  matrix metallopeptidase 8 (neutrophil...

Homo sapiens

Synonyms: CLG1, HNC, MMP-8, Matrix metalloproteinase-8, Neutrophil collagenase, ...
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Disease relevance of MMP8


Psychiatry related information on MMP8

  • The MMP-8 mRNA levels were statistically significantly increased at 8 weeks after smoking cessation compared with the baseline (p<0.05) [5].

High impact information on MMP8

  • The discovery of hydrogen isocyanide (HNC) in comet Hyakutake with an abundance (relative to hydrogen cyanide, HCN) similar to that seen in dense interstellar clouds raised the possibility that these molecules might be surviving interstellar material [6].
  • Moreover, comets may have supplied a substantial fraction of the volatiles on the terrestrial planets, perhaps including organic compounds that played a role in the origin of life on Earth. Here we report the detection of hydrogen isocyanide (HNC) in comet Hyakutake [7].
  • The HNC, H2CO, H2S, and CS abundances relative to H2O measured during breakup are consistent with those obtained in other comets [8].
  • Spectra obtained from ground-based radio telescopes show the progressive release of CO, CH3OH, HCN, H2O (from OH), H2S, CS, H2CO, CH3CN, and HNC as comet Hale-Bopp (C/1995 01) approached the sun from 6.9 to 1.4 astronomical units (AU) [9].
  • Based on their size relative to characterized products of an MMP-8 digest (Fosang, A.J., K. Last, P. Gardiner, D.C. Jackson, and L. Brown. 1995, Biochem. J. 310:337-343), these AF-28 fragments were derived from proteinase cleavage at, or near, the ...ITEGE373 / ARGSV... aggrecanase site [10].

Chemical compound and disease context of MMP8


Biological context of MMP8


Anatomical context of MMP8


Associations of MMP8 with chemical compounds

  • MMP-8 and truncated MMP-8 were sensitive to inhibition by 30 microM doxycycline, while MMP-1 was slightly inhibited (14%) by 90 microM doxycycline [18].
  • The two additional phenyl and piperidyl ring substituents of the inhibitor bind into the S1' and S2' pockets of MMP-8, respectively [19].
  • The crystal structure of the complex with MMP-8 shows that the N-hydroxyurea, contrary to the analogous hydroxamate, binds the catalytic zinc ion in a monodentate rather than bidentate mode and with high out-of-plane distortion of the amide bonds [22].
  • Matrix metalloproteinase-8 expression was evidenced in the colon surface epithelial cells and the protein was more abundant in dextran sulfate sodium-induced mice colon [23].
  • Pretreatment of skin with the glucocorticoid clobetasol, but not all-trans retinoic acid, significantly blocked ultraviolet-induced increases in MMP-8 protein levels, and neutrophil infiltration [24].

Physical interactions of MMP8


Enzymatic interactions of MMP8

  • MMP-8 cleaves TFPI following Ser(174) within the connecting region between the second and third Kunitz domains ( k (cat)/ K (m) approximately 75 M(-1).s(-1)) as well as following Lys(20) within the NH(2)-terminal region [25].
  • Time course studies indicated that only following depletion of substrate containing the preferred clip site did MMP-8 rapidly cleave at the aggrecanase site [27].
  • Recombinant human MMP-8 catalytic domain cleaved native aggrecan in a concentration-related manner between 0.2 and 2 microg/ml, with complete release of glycosaminoglycan at 2 microg/ml or greater [27].

Regulatory relationships of MMP8


Other interactions of MMP8

  • Fibrillar type I collagen was cleaved with comparable efficiency to the fibroblast and neutrophil collagenases (MMP-1 and MMP-8), respectively [31].
  • CONCLUSION: Significant inhibition of MMP-13 and MMP-8 activity against collagen occurred in vitro at concentrations that were near the concentrations achieved in serum after oral dosing [18].
  • These changes were reflected by enhanced cleavage of the MT1-LCD-bound collagen by the collagenases MMP-1 and MMP-8 but not by trypsin or MMP-7 [32].
  • Plasma MMP-9 increased by over 400% and MMP-8 by over 100% from baseline values by 12 h post-MI (p < 0.05 vs. baseline) [33].
  • MMP-3 and MMP-8 message was up-regulated in the damaged cartilage from both joints, or if the tissue was cultured in the presence of IL-1beta [34].

Analytical, diagnostic and therapeutic context of MMP8


  1. Membrane-bound matrix metalloproteinase-8 on activated polymorphonuclear cells is a potent, tissue inhibitor of metalloproteinase-resistant collagenase and serpinase. Owen, C.A., Hu, Z., Lopez-Otin, C., Shapiro, S.D. J. Immunol. (2004) [Pubmed]
  2. Cytokine-regulated expression of collagenase-2 (MMP-8) is involved in the progression of ovarian cancer. Stadlmann, S., Pollheimer, J., Moser, P.L., Raggi, A., Amberger, A., Margreiter, R., Offner, F.A., Mikuz, G., Dirnhofer, S., Moch, H. Eur. J. Cancer (2003) [Pubmed]
  3. Neutrophil collagenase (MMP-8) is expressed during early development in neural crest cells as well as in adult melanoma cells. Giambernardi, T.A., Sakaguchi, A.Y., Gluhak, J., Pavlin, D., Troyer, D.A., Das, G., Rodeck, U., Klebe, R.J. Matrix Biol. (2001) [Pubmed]
  4. Matrix metalloproteinase 8 (neutrophil collagenase) in the pathogenesis of abdominal aortic aneurysm. Wilson, W.R., Schwalbe, E.C., Jones, J.L., Bell, P.R., Thompson, M.M. The British journal of surgery. (2005) [Pubmed]
  5. Alterations of gene expression in human neutrophils induced by smoking cessation. Morozumi, T., Kubota, T., Sugita, N., Itagaki, M., Yoshie, H. Journal of clinical periodontology. (2004) [Pubmed]
  6. Chemical processing in the coma as the source of cometary HNC. Irvine, W.M., Bergin, E.A., Dickens, J.E., Jewitt, D., Lovell, A.J., Matthews, H.E., Schloerb, F.P., Senay, M. Nature (1998) [Pubmed]
  7. Spectroscopic evidence for interstellar ices in comet Hyakutake. Irvine, W.M., Bockelee-Morvan, D., Lis, D.C., Matthews, H.E., Biver, N., Crovisier, J., Davies, J.K., Dent, W.R., Gautier, D., Godfrey, P.D., Keene, J., Lovell, A.J., Owen, T.C., Phillips, T.G., Rauer, H., Schloerb, F.P., Senay, M., Young, K. Nature (1996) [Pubmed]
  8. Outgassing behavior and composition of comet C/1999 S4 (LINEAR) during its disruption. Bockelée-Morvan, D., Biver, N., Moreno, R., Colom, P., Crovisier, J., Gérard, E., Henry, F., Lis, D.C., Matthews, H., Weaver, H.A., Womack, M., Festou, M.C. Science (2001) [Pubmed]
  9. Evolution of the outgassing of comet Hale-Bopp (C/1995 O1) from radio observations. Biver, N., Bockelée-Morvan, D., Colom, P., Crovisier, J., Davies, J.K., Dent, W.R., Despois, D., Gérard, E., Lellouch, E., Rauer, H., Moreno, R., Paubert, G. Science (1997) [Pubmed]
  10. Aggrecan is degraded by matrix metalloproteinases in human arthritis. Evidence that matrix metalloproteinase and aggrecanase activities can be independent. Fosang, A.J., Last, K., Maciewicz, R.A. J. Clin. Invest. (1996) [Pubmed]
  11. Reduction of matrix metalloproteinase 8-neutrophil collagenase levels during long-term doxycycline treatment of reactive arthritis. Lauhio, A., Konttinen, Y.T., Tschesche, H., Nordström, D., Salo, T., Lähdevirta, J., Golub, L.M., Sorsa, T. Antimicrob. Agents Chemother. (1994) [Pubmed]
  12. Changes in MMP-2 and -9 activity and MMP-8 reactivity after amphotericin B induced synovitis and treatment with bufexamac. Marttinen, P.H., Raulo, S.M., Suominen, M.M., Tulamo, R.M. Journal of veterinary medicine. A, Physiology, pathology, clinical medicine. (2006) [Pubmed]
  13. Granulocyte elastase, matrix metalloproteinase-8 and prostaglandin E2 in gingival crevicular fluid in matched clinical sites in smokers and non-smokers with persistent periodontitis. Söder, B., Jin, L.J., Wickholm, S. Journal of clinical periodontology. (2002) [Pubmed]
  14. Gingival crevicular fluid matrix metalloproteinase-8 levels following adjunctive use of meloxicam and initial phase of periodontal therapy. Buduneli, N., Vardar, S., Atilla, G., Sorsa, T., Luoto, H., Baylas, H. J. Periodontol. (2002) [Pubmed]
  15. Chemotherapy of advanced head and neck cancer: updated results of a randomized trial of the order of administration of sequential methotrexate and 5-fluorouracil. Mackintosh, J.F., Coates, A.S., Tattersall, M.H., Swanson, C. Med. Pediatr. Oncol. (1988) [Pubmed]
  16. Functionally significant SNP MMP8 promoter haplotypes and preterm premature rupture of membranes (PPROM). Wang, H., Parry, S., Macones, G., Sammel, M.D., Ferrand, P.E., Kuivaniemi, H., Tromp, G., Halder, I., Shriver, M.D., Romero, R., Strauss, J.F. Hum. Mol. Genet. (2004) [Pubmed]
  17. The correlation between difference in foreign body reaction between implant locations and cytokine and MMP expression. Luttikhuizen, D.T., van Amerongen, M.J., de Feijter, P.C., Petersen, A.H., Harmsen, M.C., van Luyn, M.J. Biomaterials (2006) [Pubmed]
  18. Specificity of inhibition of matrix metalloproteinase activity by doxycycline: relationship to structure of the enzyme. Smith, G.N., Mickler, E.A., Hasty, K.A., Brandt, K.D. Arthritis Rheum. (1999) [Pubmed]
  19. The 1.8-A crystal structure of a matrix metalloproteinase 8-barbiturate inhibitor complex reveals a previously unobserved mechanism for collagenase substrate recognition. Brandstetter, H., Grams, F., Glitz, D., Lang, A., Huber, R., Bode, W., Krell, H.W., Engh, R.A. J. Biol. Chem. (2001) [Pubmed]
  20. Differential patterns of response to doxycycline and transforming growth factor beta1 in the down-regulation of collagenases in osteoarthritic and normal human chondrocytes. Shlopov, B.V., Smith, G.N., Cole, A.A., Hasty, K.A. Arthritis Rheum. (1999) [Pubmed]
  21. Response of matrix metalloproteinases and tissue inhibitors of metalloproteinases messenger ribonucleic acids to ovarian steroids in human endometrial explants mimics their gene- and phase-specific differential control in vivo. Vassilev, V., Pretto, C.M., Cornet, P.B., Delvaux, D., Eeckhout, Y., Courtoy, P.J., Marbaix, E., Henriet, P. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  22. N-Hydroxyurea as zinc binding group in matrix metalloproteinase inhibition: mode of binding in a complex with MMP-8. Campestre, C., Agamennone, M., Tortorella, P., Preziuso, S., Biasone, A., Gavuzzo, E., Pochetti, G., Mazza, F., Hiller, O., Tschesche, H., Consalvi, V., Gallina, C. Bioorg. Med. Chem. Lett. (2006) [Pubmed]
  23. Gelatinase A (MMP-2), collagenase-2 (MMP-8), and laminin-5 gamma2-chain expression in murine inflammatory bowel disease (ulcerative colitis). Pirilä, E., Ramamurthy, N.S., Sorsa, T., Salo, T., Hietanen, J., Maisi, P. Dig. Dis. Sci. (2003) [Pubmed]
  24. Ultraviolet irradiation increases matrix metalloproteinase-8 protein in human skin in vivo. Fisher, G.J., Choi, H.C., Bata-Csorgo, Z., Shao, Y., Datta, S., Wang, Z.Q., Kang, S., Voorhees, J.J. J. Invest. Dermatol. (2001) [Pubmed]
  25. Structural and functional characterization of tissue factor pathway inhibitor following degradation by matrix metalloproteinase-8. Cunningham, A.C., Hasty, K.A., Enghild, J.J., Mast, A.E. Biochem. J. (2002) [Pubmed]
  26. Preparation of active recombinant TIMP-1 from Escherichia coli inclusion bodies and complex formation with the recombinant catalytic domain of PMNL-collagenase. Kleine, T., Bartsch, S., Bläser, J., Schnierer, S., Triebel, S., Valentin, M., Gote, T., Tschesche, H. Biochemistry (1993) [Pubmed]
  27. Cleavage of native cartilage aggrecan by neutrophil collagenase (MMP-8) is distinct from endogenous cleavage by aggrecanase. Arner, E.C., Decicco, C.P., Cherney, R., Tortorella, M.D. J. Biol. Chem. (1997) [Pubmed]
  28. Increased activity of matrix metalloproteinase-8 and matrix metalloproteinase-9 in induced sputum from patients with COPD. Vernooy, J.H., Lindeman, J.H., Jacobs, J.A., Hanemaaijer, R., Wouters, E.F. Chest (2004) [Pubmed]
  29. Expression and induction of collagenases (MMP-8 and -13) in plasma cells associated with bone-destructive lesions. Wahlgren, J., Maisi, P., Sorsa, T., Sutinen, M., Tervahartiala, T., Pirilä, E., Teronen, O., Hietanen, J., Tjäderhane, L., Salo, T. J. Pathol. (2001) [Pubmed]
  30. The expression of MMP-8 in human odontoblasts and dental pulp cells is down-regulated by TGF-beta1. Palosaari, H., Wahlgren, J., Larmas, M., Rönkä, H., Sorsa, T., Salo, T., Tjäderhane, L. J. Dent. Res. (2000) [Pubmed]
  31. Biochemical characterization of human collagenase-3. Knäuper, V., López-Otin, C., Smith, B., Knight, G., Murphy, G. J. Biol. Chem. (1996) [Pubmed]
  32. Characterization of the distinct collagen binding, helicase and cleavage mechanisms of matrix metalloproteinase 2 and 14 (gelatinase A and MT1-MMP): the differential roles of the MMP hemopexin c domains and the MMP-2 fibronectin type II modules in collagen triple helicase activities. Tam, E.M., Moore, T.R., Butler, G.S., Overall, C.M. J. Biol. Chem. (2004) [Pubmed]
  33. Release of matrix metalloproteinases following alcohol septal ablation in hypertrophic obstructive cardiomyopathy. Bradham, W.S., Gunasinghe, H., Holder, J.R., Multani, M., Killip, D., Anderson, M., Meyer, D., Spencer, W.H., Torre-Amione, G., Spinale, F.G. J. Am. Coll. Cardiol. (2002) [Pubmed]
  34. Expression of matrix metalloproteinases in normal and damaged articular cartilage from human knee and ankle joints. Chubinskaya, S., Kuettner, K.E., Cole, A.A. Lab. Invest. (1999) [Pubmed]
  35. Matrix metalloproteinase (MMP)-8 and MMP-9 in cerebrospinal fluid during bacterial meningitis: association with blood-brain barrier damage and neurological sequelae. Leppert, D., Leib, S.L., Grygar, C., Miller, K.M., Schaad, U.B., Holländer, G.A. Clin. Infect. Dis. (2000) [Pubmed]
  36. Matrix metalloproteinases and tissue inhibitor of metalloproteinase-1 in sarcoidosis and IPF. Henry, M.T., McMahon, K., Mackarel, A.J., Prikk, K., Sorsa, T., Maisi, P., Sepper, R., Fitzgerald, M.X., O'Connor, C.M. Eur. Respir. J. (2002) [Pubmed]
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