Author/Editor		Lah, Tamara; Babnik, Joža; Skalerič, Uroš; Turk, Vito
Title		Lysosomal proteolysis in inflammation
Translated title		Lizosomalna proteoliza pri vnetju
Type		članek
Source		Zdrav Vestn
Vol. and No.		Letnik 67, št. Suppl 2
Publication year		1998
Volume		str. II-29-32
Language		eng
Abstract		Host response to pathogen invasion of gingiva involves the accumulation of neutrophils and macrophages at the site of acute inflammation, with the release, among other biological active molecules, of lysosomal proteolytic enzymes, including cathepsins G, D, B, L, H and possibly others. In addition, the expression of their endogenous inhibitors, produced locally or systemically, is altered resulting in an imbalance between proteinases and inhibitors. When the host proteolytic cascades are activated by the pathogens to their advantage, the disease becomes chronic, resulting in substantial loss of periodontal tissue and alveolar bone. Our investigations of patients with acute and chronic periodontitis have demonstrated that, as well as metalloproteinases, cysteine proteinases, cathepsine B, L and H and their endogenous inhibitors, such as tissue derived stefins A and B, cystatin C, kininogens, a variety of salivary cystatins (S, SN, SA) and alpha-2 marcroglobulin, play an active reole in the process. Biological components of the cysteine-dependent host proteolytic system, highly upregulated in inflamed tissue and secreted into gingival fluid, may provide a potential diagnostic tool for prognosis of advanced periodontitis. The inhibitors of cysteine proteinases may prove as therapeutic agents in later stages of the disease, possibly, applied in combination with inhibitorst of pathogenic agents.
Summary		Invazija patogenih organizmov, od katerih je Porphyromonas gingivalis najbolj pogosta bakterija v zobnih oblogah, sproži odgovor gostitelja v dlesni in vključuje dotok belih krvničk, nevtrofilcev in makrofagov, ki na mesto vnetja sproščajo, med ostalimi biološko aktivnimi proteini, tudi lisozomalne encime katepsine G, D, B, L in H. Poleg bakterijskih metalo in serinskih proteinaz, je bakterijska cisteinska proteinaza gingipain ključnega pomena tako pri sproženju proteoliznih kaskad, kakor tudi pri neposredni razgradnji tkiv in pri proteoliznem moduliranju drugih proteinov, ki so vpleteni v vnetni proces. Aktivnosti proteinaze gostitelja regulirajo proteinazni inhibitorji, ki pa jih bakterijske proteinaze, superoksidni antioni in vodikov peroksid, ki se sproščajo v dlesen v začetni fazi vnetja, inaktivirajo. To močno poviša aktivnost nevrofilne elastaze in katepsina G. Elastaza razgrajuje endogene inhibitorje, tako tkivnih metalo-proteinaz (kolagenaz, gelatinaz), kakor cisteinskih katepsinov B in L. Aktivnost teh se tako ob naraščajoči vsebnosti makrofagov, ki so glavni vir teh encimov, povečuje. Tudi katepsin D, ki se sprošča iz makrofagov pri procesih fagocitoze, razgrajuje inhibitorje cisteinskih katepsinov, cistatine, stefine in kininogene, kar še bolj zvišuje aktivnost katepsinov B in L. Spremembe v lokalni ali sistemski ekspresiji endogenih proteinaz in inhibitorjev vodijo do neravnotežja, ki močno poveča proteolizni potencial v dlesni. Ko torej patogeni organizmi uspejo aktivirati proteolizne sisteme gostitelja tako, da ti delujejo v njihovo korist, se bolezni iz akutne preusmeri v kronično, z naraščajočo razgradnjo dlesni in čeljustne kosti. Naše raziskave pacientov s paradontalno boleznijo so pokazale na pomembne spremembe vsebnosti katepsiov B, L in H ter njihovih endogenih inhibitorjev, stefina A in B, cistatina C, kininogena in vrste cistatinov v slini (cistatin S, SA in SN).(Izvleček prekinjen pri 2000 znakih.)
Descriptors		INFLAMMATION PERIODONTITIS CATHEPSINS PROTEASE INHIBITORS LYSOSOMES INFLAMMATION MEDIATORS PORPHYROMONAS GINGIVALIS ASPARTIC PROTEINASES CYSTEINE PROTEINASES