PMID- 9933437 OWN - NLM STAT- MEDLINE DCOM- 19990218 LR - 20220311 IS - 0009-9104 (Print) IS - 1365-2249 (Electronic) IS - 0009-9104 (Linking) VI - 115 IP - 1 DP - 1999 Jan TI - CD40 engagement modulates the production of matrix metalloproteinases by gingival fibroblasts. PG - 161-7 AB - Chronic periodontitis is a destructive inflammatory disease linked with unbalanced production between matrix metalloproteinases (MMPs), such as interstitial collagenase (MMP-1) and stromelysin-1 (MMP-3) and their endogenous tissue inhibitors of MMPs (TIMPs). In addition to aberrant MMP-1 and MMP-3 expression, periodontal lesions are characterized by dense infiltrations of activated T lymphocytes which may interact with CD40-expressing gingival fibroblasts in the connective tissue via the CD40L-CD40 pathway. In this study we investigated whether CD40 cross-linking influenced MMP production by gingival fibroblasts. Therefore, we analysed the CD40L-induced MMP production by these fibroblasts in the presence of cytokines that are increased in periodontal lesions, such as IL-1beta, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). We show that CD40 ligation on gingival fibroblasts resulted in a decrease of their MMP-1 and MMP-3 production, while MMP-2 and TIMP-1 production were unaffected as determined by Western blot. This down-regulatory effect of CD40 engagement on MMP-1 and MMP-3 production by gingival fibroblasts was also present when MMP production was up-regulated by IL-1beta and TNF-alpha or down-regulated by IFN-gamma. These results suggest that CD40 ligation on gingival fibroblasts leads to a restraining of MMP-1 and MMP-3 production by gingival fibroblasts and thereby may be an important mechanism in the retardation of further periodontal tissue damage. FAU - Wassenaar, A AU - Wassenaar A AD - Department of Cell Biology and Histology, Academic Medical Centre (AMC), University of Amsterdam, The Netherlands. FAU - Verschoor, T AU - Verschoor T FAU - Kievits, F AU - Kievits F FAU - Den Hartog, M T AU - Den Hartog MT FAU - Kapsenberg, M L AU - Kapsenberg ML FAU - Everts, V AU - Everts V FAU - Snijders, A AU - Snijders A LA - eng PT - Journal Article PL - England TA - Clin Exp Immunol JT - Clinical and experimental immunology JID - 0057202 RN - 0 (CD40 Antigens) RN - 0 (Interleukin-1) RN - 0 (Interleukin-6) RN - 0 (Interleukin-8) RN - 0 (Tumor Necrosis Factor-alpha) RN - 82115-62-6 (Interferon-gamma) RN - EC 3.4.24.- (Metalloendopeptidases) SB - IM MH - Adult MH - CD40 Antigens/*physiology MH - Extracellular Matrix/*enzymology MH - Fibroblasts/metabolism/*physiology MH - Gingiva/*cytology MH - Humans MH - Interferon-gamma/pharmacology MH - Interleukin-1/pharmacology MH - Interleukin-6/metabolism MH - Interleukin-8/metabolism MH - Metalloendopeptidases/*biosynthesis MH - Tumor Necrosis Factor-alpha/pharmacology PMC - PMC1905194 EDAT- 1999/02/05 00:00 MHDA- 1999/02/05 00:01 PMCR- 2000/01/01 CRDT- 1999/02/05 00:00 PHST- 1999/02/05 00:00 [pubmed] PHST- 1999/02/05 00:01 [medline] PHST- 1999/02/05 00:00 [entrez] PHST- 2000/01/01 00:00 [pmc-release] AID - 10.1046/j.1365-2249.1999.00764.x [doi] PST - ppublish SO - Clin Exp Immunol. 1999 Jan;115(1):161-7. doi: 10.1046/j.1365-2249.1999.00764.x.