Disease relevance of MMP8

• Thus, MMP-8 has an unexpected, anti-inflammatory role during acute lung injury in mice [1].
• TIMP-resistant, active MMP-8 expressed on the surface of activated PMN is likely to be an important form of MMP-8, regulating lung inflammation and collagen turnover in vivo [1].
• The aim of our study was to determine MMP-8 expression and regulation in ovarian cancer and its association with other MMPs and tissue inhibitors of metalloproteinases (TIMPs) [2].
• In a previous study, we observed MMP-8 expression in human melanoma cells [3].
• Matrix metalloproteinase 8 (neutrophil collagenase) in the pathogenesis of abdominal aortic aneurysm [4].

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

• The aim of this work was to determine whether human polymorphonuclear neutrophilic interstitial collagenase (matrix metalloproteinase 8 [MMP-8]) levels are reduced during long-term doxycycline treatment in humans with reactive arthritis [11].
• Changes in MMP-2 and -9 activity and MMP-8 reactivity after amphotericin B induced synovitis and treatment with bufexamac [12].
• Granulocyte elastase, matrix metalloproteinase-8 and prostaglandin E2 in gingival crevicular fluid in matched clinical sites in smokers and non-smokers with persistent periodontitis [13].
• BACKGROUND: The purpose of the present study was to assess the effects of adjunctive meloxicam on the matrix metalloproteinase-8 (MMP-8) levels of gingival crevicular fluid (GCF) in chronic periodontitis patients following the initial phase of periodontal therapy [14].
• One hundred and twenty-seven patients with advanced or recurrent squamous cell carcinoma of the head and neck (HNC) were randomized to treatment with methotrexate (MTX) followed 1 hour later by 5-fluorouracil (5-FU) (sequence MF), or 5-fluorouracil followed after 1 hour by methotrexate (sequence FM) [15].

Biological context of MMP8

• These findings demonstrate the functional significance of SNP haplotypes in the MMP8 gene and associations with obstetrical outcomes [16].
• We identified three single nucleotide polymorphisms (SNPs) at -799C/T, -381A/G and +17C/G from the major transcription start site in the MMP8 gene, and determined the functional significance of these SNPs by analyzing their impact upon MMP8 promoter activity and their association with preterm premature rupture of membranes (PPROM) [16].
• The gene expression levels of collagen degrading MMPs, i.e. MMP8, MMP13 and MMP14 were similar in subcutaneous and supra-epicardial disks [17].
• Studies with truncated enzymes and 2 substrates suggest that doxycycline disrupts the conformation of the hemopexin-like domain of MMP-13 and the catalytic domain of MMP-8 [18].
• RO200-1770 induces a major rearrangement at a position relevant to substrate recognition near the MMP-8 active site (Ala206-Asn218) [19].

Anatomical context of MMP8

• Functionally significant SNP MMP8 promoter haplotypes and preterm premature rupture of membranes (PPROM) [16].
• Matrix metalloproteinase 8 (MMP8), an enzyme that degrades fibrillar collagens imparting strength to the fetal membranes, is expressed by leukocytes and chorionic cytotrophoblast cells [16].
• Based on the 1.8-A crystal structure of human neutrophil collagenase (MMP-8) in complex with an active site-directed inhibitor (RO200-1770), we identify and describe new structural determinants for substrate and inhibitor recognition in addition to the primary substrate recognition sites [19].
• In contrast, chondrocytes from areas located more distant from the macroscopic lesion increased MMP-13 mRNA, while MMP-1 and MMP-8 decreased after stimulation with TGFbeta1 [20].
• Finally, in situ hybridization evidenced the major contribution of fibroblasts to the increase in MMP-8 mRNA at menstruation or in explants cultured without hormones [21].

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

• (125)I-factor Xa ligand blots of TFPI fragments generated following MMP-8 degradation were used for probing binding interactions between factor Xa and regions of TFPI, other than the second Kunitz domain [25].
• Preparation of active recombinant TIMP-1 from Escherichia coli inclusion bodies and complex formation with the recombinant catalytic domain of PMNL-collagenase [26].

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

• Increased activity of matrix metalloproteinase-8 and matrix metalloproteinase-9 in induced sputum from patients with COPD [28].
• Since MMP-13 was more frequently expressed than MMP-8 in plasma cells of strongly recurring keratocysts and malignant plasmacytomas, it is concluded that plasma cell MMP-13 has a particularly important role in benign and malignant bone-destructive lesions [29].
• TGF-beta down-regulated the MMP-8 mRNA and concentration of secreted protein in both cultures [30].

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

• Immunohistochemistry was used to localize MMP-8 expression [4].
• In addition, MMP-8 expression in vitro was analysed by a specific immunoassay and PCR-analysis [2].
• RT-PCR analysis of post-implantation mouse embryos indicated the presence of MMP-8 transcripts at E9 [3].
• Repeated lumbar punctures showed that levels of MMP-8 and MMP-9 were regulated independently and did not correlate with the CSF cell count [35].
• Western immunoblotting revealed the presence of two isoforms of MMP-8 in patient samples; an 80 kD form representing latent enzyme from polymorphonuclear neutrophils and a 55 kD form representing the fibroblast-type proform [36].

References