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Matrix metalloproteinase-2 and -9 activity levels increase in cutaneous lupus erythematosus lesions and correlate with disease severity

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Abstract

Lupus erythematosus is a chronic autoimmune disease characterized by remissions and exacerbations. Accumulated evidence indicated that matrix metalloproteinases (MMPs) are upregulated in inflammatory cells of cutaneous lupus erythematosus (CLE); however, the activity levels of these proteases have remained uncharacterized. To elucidate the significance of MMP-2, MMP-9, and TIMP-1 in CLE pathogenesis, gelatin zymography was used to investigate pro and active levels of MMP-2 and MMP-9 in lesional and perilesional skin biopsies obtained from twenty-two CLE patients. TIMP-1 protein levels were detected by ELISA in the biopsy specimens. The correlation between biochemical parameters and clinical characteristics of the disease was also evaluated. Significantly higher levels of active MMP-2, active MMP-9, proMMP-9, active/proMMP-2, and TIMP-1 were detected in lesional skin samples. Besides, the active/proMMP-9 was elevated in female and smoking patients. Active MMP-9 levels and active/proMMP-9 were also increased in elderly patients. Active MMP-9 levels were lower in patients who had smaller total damage score. Consistently, active/proMMP-9 and active/proMMP-2 were positively correlated with CLASI. Interestingly, in hydroxychloroquine or topical corticosteroid-treated patients, MMP-2/-9 activity levels were found to be higher compared to untreated patients. These findings suggest that increased MMP-2 and MMP-9 activities may contribute to the pathogenesis of CLE and cutaneous disease severity.

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Abbreviations

LE:

Lupus erythematosus

SLE:

Systemic lupus erythematosus

CLE:

Cutaneous lupus erythematosus

SCLE:

Subacute cutaneous lupus erythematosus

DLE:

Discoid lupus erythematosus

MMP:

Matrix metalloproteinase

TIMP:

Tissue inhibitor of metalloproteinases

CLASI:

Lupus erythematosus disease area and severity index

SDS:

Sodium dodecyl sulfate

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Funding

This research was supported in part by a Grant (2011.KB.SAĞ.10) from Dokuz Eylul University Scientific Research Project Coordination Unit.

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Author notes

  1. Goksen Ertuğrul and Didem Keles contributed equally to this work (co-first authorship).

Authors and Affiliations

  1. Department of Dermatology and Venereology, School of Medicine, Dokuz Eylul University, 35340, Inciralti, Izmir, Turkey

    Goksen Ertugrul & Sebnem Aktan

  2. Department of Medical Biochemistry, School of Medicine, Dokuz Eylul University, 35340, Inciralti, Izmir, Turkey

    Didem Keles & Gulgun Oktay

  3. Department of Dermatology and Venereology, Karabük University Training and Research Hospital, 78200, Karabük, Turkey

    Goksen Ertugrul

Authors
  1. Goksen Ertugrul
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  2. Didem Keles
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Correspondence to Goksen Ertugrul.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Informed consent was obtained from all individual participants included in the study.

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Ertugrul, G., Keles, D., Oktay, G. et al. Matrix metalloproteinase-2 and -9 activity levels increase in cutaneous lupus erythematosus lesions and correlate with disease severity. Arch Dermatol Res 310, 173–179 (2018). https://doi.org/10.1007/s00403-018-1811-2

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  • DOI: https://doi.org/10.1007/s00403-018-1811-2

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