In vivo inhibition of human neutrophil collagenase (MMP-8) activity during long-term combination therapy of doxycycline and non-steroidal anti-inflammatory drugs (NSAID) in acute reactive arthritis

Lauhio, Anneli; Salo, Tuula; Ding, Yanli; Konttinen, Y T; Nordström, Dan; Tschesche, Harald; Lähdevirta, Juhani; Lm, Golub; Sorsa, Timo

doi:10.1111/j.1365-2249.1994.tb06601.x

Cited by 72 publications

(32 citation statements)

References 31 publications

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“…The results of the present work demonstrating that upregulation of MMP-8 is associated with poor outcome further suggest that the therapy of disseminated LB should include also MMP-8 inhibitor. Doxycycline and other tetracycline group of antibiotics such as lymecycline have been shown to act as MMP-8 inhibitor and down-regulator by several mechanisms both in vitro and in vivo [15][16][17][18][19][20]. On the basis of the present results together with findings by Hu and coworkers [11] we suggest that doxycycline as MMP-8 inhibitor should be included in the treatment of disseminated LB.…”

Section: Figure 4 (A)supporting

confidence: 70%

“…The results of the present work showing that among these patients suffering from persistent joint symptoms after betalactam antibiotic treatment high serum MMP-8 was associated with poor outcome suggest that the treatment of the patients having persisting symptoms after betalactam antibiotics should include doxycycline as an MMP-8 inhibitor. It is likely that due to rebound effect a short one week course will not be sufficient [21], but instead a longer treatment with doxycycline would be needed [15,18,19]. In addition, the results of this work suggest that serum MMP-8 assessment could possibly be useful in the monitoring of the effectiveness of the therapy [22].…”

Section: Figure 4 (A)mentioning

confidence: 91%

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Serum Matrix Metalloproteinase-8 and -9 Levels in Disseminated Lyme Borreliosis with Special Reference to Arthritis

Lauhio¹,

Oksi²,

Tervahartiala³

et al. 2012

BIO

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Recent evidence suggests that matrix metalloproteinases (MMPs) are involved in pathogenesis of Lyme borreliosis (LB). We studied serum levels of MMP-8 and MMP-9 in disseminated LB patients with special reference to arthritis. Serum MMP-8 and-9 levels were analyzed by enzyme-linked immunoabsorbent assay from 110 patients from our previous multicenter, prospective study. Serum samples were taken before betalactam antibiotic treatment at study entry and after antibiotic treatment, at 1 year follow-up.Among disseminated LB patients (n = 110) mean (± SEM) serum MMP-8 and -9 levels (ng/ml) at study entry were statistically significantly higher than at 1 year follow-up (28.0 ± 1.9 versus 23.1 ± 1.6, P = 0.0313 and 398.0 ± 22.7 vs. 334.3 ± 23.6, P = 0.0219, respectively). Among Lyme arthritis (LA) patients (n = 34) at study entry serum MMP-8, but not MMP-9, levels decreased significantly when compared to serum levels of those at 1 year follow-up (35.7 ± 4.4 vs. 22.4 ± 2.3, P = 0.0093 and 398.6 ± 44.1 vs. 297.8 ± 40.3, P = 0.0505, respectively). The mean (± SEM) serum levels (ng/ml) of MMP-8 were significantly higher after betalactam antibiotic treatment at 1 year follow-up among antibiotic resistant LA patients with poor response than among those LA patients who were totally recovered (32.8 ± 6.4 vs. 20.1 ± 2.3, P = 0.0376). In contrast, the mean (± SEM) serum levels (ng/ml) of MMP-9 of antibiotic resistant LA patients showed no statistical significant difference when compared to those LA patients who were totally recovered at 1 year follow-up (297.8 ± 40.3 vs. 396.8 ± 93.9, P = 0.80).In conclusion, our results suggest that serum MMP-8 levels are excessively upregulated in disseminated LB contributing to inflammatory response, and related to persistent joint symptoms. This novel finding may offer in the future new laboratory possibilities to diagnose patients with persistent symptoms after betalactam antibiotic treatment. In addition the present findings suggest that to improve the outcome of disseminated borreliosis, the therapy of disseminated LB should include MMP-8 inhibitor such as doxycycline, possibly in combination therapy such as a combination of ceftriaxone and doxycycline. BIO © [2012], Copyright CCAAS Anneli Lauhio, et. al., BIO 2012, 2, 68-74 69 http://ccaasmag.org/BIO

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Section: Figure 4 (A)supporting

confidence: 70%

Section: Figure 4 (A)mentioning

confidence: 91%

Serum Matrix Metalloproteinase-8 and -9 Levels in Disseminated Lyme Borreliosis with Special Reference to Arthritis

Lauhio¹,

Oksi²,

Tervahartiala³

et al. 2012

BIO

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“…Immunoblot was used as described previously (14,15). Briefly, samples were mixed with Laemmli buffer without reducing agents and heated for 5 min at 100-C, followed by protein separation by 10% SDS-polyacrylamide gels.…”

Section: Western Immunoblottingmentioning

confidence: 99%

“…The immunoblots were quantified by Bio-Rad Model GS-700 Imaging Densitometer using the Molecular Analysis program (Bio-Rad Laboratories, Inc., Hercules, CA, USA). Human rheumatoid synovial fibroblast culture medium was used as positive control to distinguish neutrophil-type MMP-8 from fibroblast/mesenchymal-type MMP-8 as well as for MMP-1 and MMP-13 (14,15).…”

Section: Western Immunoblottingmentioning

confidence: 99%

Collagenase 2/Matrix Metalloproteinase 8 in Critically Ill Patients With Secondary Peritonitis

Hästbacka

Hynninen²,

Kolho³

et al. 2007

Shock

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Secondary peritonitis is an important indication for surgical intensive care admissions, and it is associated with high morbidity and mortality. Collagenase 2/matrix metalloproteinase (MMP) 8 is a tissue matrix-degrading enzyme that is released from leukocytes upon inflammatory stimuli and may thus contribute to peritonitis-associated organ damage. We studied the levels and activity of MMP-8 in the peritoneal fluid of 15 critically ill patients with secondary peritonitis. The MMP-8 levels were measured from the patients' peritoneal fluid, serum, and urine, and from the serum and urine of 10 healthy controls by immunofluorometric assay. Median MMP-8 level in peritoneal fluid supernatant was 1,317 microg/L (interquartile range [IQR]) (1,254-1,359 microg/L) being significantly higher than in the sera of the patients (P=0.008). Molecular forms and isoform distribution of MMP-8, MMP-1, and MMP-13 in peritoneal fluid, assessed by Western immunoblotting, revealed that the neutrophil-type MMP-8 was the major collagenase species in peritoneal fluid, and it was partially in an activated form. Catalytically competent, active MMP-8 produced the characteristic cleavage products from intact human type I collagen. The serum levels of MMP-8 were higher in the patients, 49 microg/L (IQR, 23-214 microg/L), than in the controls, 11 microg/L (IQR, 8-24 microg/L) (P<0.01). The MMP-8 levels in the urine were higher in the patients, 0.27 microg/L (IQR, 0.04-1.89 microg/L), than in the controls, 0.03 microg/L (IQR, 0.0-0.05 microg/L) (P=0.013). Our data demonstrate for the first time that MMP-8 levels are remarkably elevated and in an active and catalytically competent form in the peritoneal fluid samples of patients with secondary peritonitis.

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“…A specific polyclonal antibody raised against human MMP-8 [11,20] was used. Western blotting for MMP-8 was performed as described earlier by Määttä et al [24].…”

Section: Western Immunoblottingmentioning

confidence: 99%

Tear fluid levels of MMP-8 are elevated in ocular rosacea—treatment effect of oral doxycycline

Määttä

Kari

Tervahartiala

et al. 2006

Graefe's Arch Clin Exp Ophthalmo

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In vivo inhibition of human neutrophil collagenase (MMP-8) activity during long-term combination therapy of doxycycline and non-steroidal anti-inflammatory drugs (NSAID) in acute reactive arthritis

Cited by 72 publications

References 31 publications

Serum Matrix Metalloproteinase-8 and -9 Levels in Disseminated Lyme Borreliosis with Special Reference to Arthritis

Serum Matrix Metalloproteinase-8 and -9 Levels in Disseminated Lyme Borreliosis with Special Reference to Arthritis

Collagenase 2/Matrix Metalloproteinase 8 in Critically Ill Patients With Secondary Peritonitis

Tear fluid levels of MMP-8 are elevated in ocular rosacea—treatment effect of oral doxycycline

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