PT  - JOURNAL ARTICLE
AU  - Juliane Bartmann
AU  - Marion Frankenberger
AU  - Elfriede Nößner
AU  - Claus Neurohr
AU  - Jürgen Behr
AU  - Oliver Eickelberg
AU  - Werner Von Wulffen
TI  - Inhibition of matrix metalloproteinase-13 reduces antigen-presenting functions of murine dendritic cells<em> in vitro</em>
DP  - 2014 Sep 01
TA  - European Respiratory Journal
PG  - P1011
VI  - 44
IP  - Suppl 58
4099  - http://erj.ersjournals.com/content/44/Suppl_58/P1011.short
4100  - http://erj.ersjournals.com/content/44/Suppl_58/P1011.full
SO  - Eur Respir J2014 Sep 01; 44
AB  - Rationale: Matrix metalloproteinases (MMPs) constitute a family of zinc endopeptidases. They are mainly known to degrade extracellular matrix proteins but are also involved in other cellular functions and pathological processes. Recently, it has been demonstrated that MMP-13 is expressed in murine pulmonary dendritic cells (DCs) under baseline conditions. However, profound knowledge is lacking about the specific functions of MMP-13 in DCs and its importance under inflammatory conditions.Methods and results: For analysis of DC function, bone marrow derived DCs (BMDCs) were generated. Expression of MMP-13 was confirmed on mRNA and protein level and its activity was quantified using FRET technique. Remarkably, MMP-13 demonstrated an increase on mRNA level and enhanced activity after treatment with LPS or ovalbumin, postulating the importance of MMP-13 in inflammatory processes. In order to study the requirement of MMP-13 for the immunostimulatory functions of DCs, we used a specific MMP-13 inhibitor. No alteration could be detected in the migratory capacity of BMDCs in response to CCL-19 using the MMP-13 inhibitor in a 3D collagen invasion assay. On the contrary, inhibition of MMP-13 showed a significant decrease in the endocytosis capacity of BMDCs. Furthermore, inhibition of MMP-13 influences the adaptive immune response due to reduced T cell stimulation by DCs on MHC I and II.Conclusion: Inhibition of MMP-13 in BMDCs preserves their migration potential while decreasing their endocytosis capacity. Moreover, MMP-13 inhibition has an influence on T cell-DC interaction. Thus, MMP-13 may be a promising target for therapeutic intervention in inflammatory lung diseases.