title: Cytokines modulate routes of collagen breakdown. Review with special emphasis on mechanisms of collagen degradation in the periodontium and the burst hypothesis of periodontal disease progression.
abstract: In this paper, we review recent work on collagen degradation, 2 main routes of breakdown are described and their relevance during healthy and inflammatory conditions of the periodontium is discussed. Special attention is paid to the possible role of cytokines, in particular interleukin 1 (IL-1) and transforming growth factor beta (TGF-beta), on the modulation of collagen phagocytosis and metalloproteinase production. IL-1 has been shown to have a dual function in collagen digestion. It inhibits the intracellular phagocytic pathway, but at the same time, it strongly promotes extracellular digestion by inducing the release of collagenolytic enzymes like collagenase. TGF-beta has an opposite effect on both pathways and antagonizes IL-1. Collagenase is released in an inactive form, and a considerable fraction of the proenzyme may become incorporated in the extracellular matrix. This reservoir of latent enzyme can be activated (for instance by plasmin), leading to a sudden and extensive breakdown of the collagenous fibre meshwork. It is suggested that this phenomenon may also take place during progressive periodontitis and could explain an episodic nature of collagenolysis, clinically resulting in bursts of attachment loss (burst hypothesis).
authors.affiliation: Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: van der Zee
authors.forename: V
authors.initials: V
authors.lastname: Everts
authors.forename: W
authors.initials: W
authors.lastname: Beertsen
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism*; D017364:Collagenases / Q000096:biosynthesis; D016207:Cytokines / Q000502:physiology*; D018450:Disease Progression; D004789:Enzyme Activation; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D008666:Metalloendopeptidases / Q000096:biosynthesis; D018375:Neutrophil Activation; D010518:Periodontitis / Q000201:enzymology*; D010587:Phagocytosis; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D016212:Transforming Growth Factor beta; D003094:Collagen; D017364:Collagenases; D008666:Metalloendopeptidases