MMWR
Matrix metallopeptidase 8 (MMP8), also known as neutrophil collagenase, is an enzyme that in humans is encoded by the MMP8 gene. MMP8 is a member of the matrix metalloproteinase (MMP) family, which is involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis.
Structure[edit | edit source]
MMP8 is a zinc-dependent endopeptidase. The enzyme is synthesized as an inactive proenzyme, which is activated when cleaved by extracellular proteinases. The active enzyme consists of a catalytic domain and a hemopexin-like C-terminal domain, which are connected by a flexible hinge region. The catalytic domain contains a zinc ion that is essential for its enzymatic activity.
Function[edit | edit source]
MMP8 is primarily expressed in neutrophils, a type of white blood cell, and is stored in specific granules. Upon activation of neutrophils, MMP8 is released into the extracellular space where it degrades type I, II, and III collagen, which are major components of the extracellular matrix. This activity is crucial for the migration of neutrophils through tissues during inflammatory responses.
MMP8 also plays a role in modulating the inflammatory response by processing cytokines and chemokines, thereby influencing their activity. It has been implicated in various pathological conditions, including periodontitis, rheumatoid arthritis, and cancer metastasis.
Regulation[edit | edit source]
The activity of MMP8 is tightly regulated at multiple levels, including gene expression, proenzyme activation, and inhibition by tissue inhibitors of metalloproteinases (TIMPs). TIMP-1 and TIMP-2 are known to inhibit MMP8 activity by binding to its active site.
Clinical Significance[edit | edit source]
Elevated levels of MMP8 have been associated with inflammatory diseases and certain cancers. It is considered a potential biomarker for periodontal disease and has been studied as a target for therapeutic intervention in inflammatory conditions. Inhibitors of MMP8 are being explored for their potential to treat diseases characterized by excessive tissue breakdown.
Research Directions[edit | edit source]
Current research is focused on understanding the precise role of MMP8 in various diseases and developing specific inhibitors that can modulate its activity without affecting other MMPs. Studies are also investigating the use of MMP8 as a diagnostic marker for inflammatory diseases and its potential role in tissue repair and regeneration.
Also see[edit | edit source]
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Contributors: Prab R. Tumpati, MD