TIMP-3: A Novel target for glucocorticoid signalling at the blood-brain barrier

Hartmann C, El-Gindi J, Lohmann C, Lischper M, Zeni P, Galla HJ

Forschungsartikel (Zeitschrift) | Peer reviewed

Zusammenfassung

Glucocorticoids (GCs) are used in the treatment of neuroinflammatory diseases such as multiple sclerosis. Several studies have demonstrated the beneficial effect of GCs on the balance between matrix metalloproteinases (MMPs) and their endogenous inhibitors, the TIMPs (tissue inhibitors of metalloproteinases). We could demonstrate that all four known TIMPs are present at the blood-brain barrier (BBB) endothelium. Hydrocortisone (HC) selectively upregulates TIMP-3 while TIMP-1, TIMP-2 and TIMP-4 were downregulated on the mRNA-level. This effect could be completely reversed by the glucocorticoid receptor inhibitor mifepristone (Mife). On the protein-level all TIMPs could be detected in the apical supernatants whereas in the isolated extracellular matrix (ECM) only TIMP-3 was found. The application of HC led to a strong enrichment of TIMP-3 in the ECM. Our findings demonstrate that HC directly targets TIMP-3 at the BBB assuming a protective role against matrix disruption and thus to guarantee the barrier integrity.

Details zur Publikation

Jahrgang / Bandnr. / Volume390
Ausgabe / Heftnr. / Issue390
Seitenbereich182-186
StatusVeröffentlicht
Veröffentlichungsjahr2009
Sprache, in der die Publikation verfasst istEnglisch
DOI10.1016/j.bbrc.2009.08.158

Autor*innen der Universität Münster

El-Gindi, Jehad Kamal
Institut für Biochemie
Galla, Hans-Joachim
Professur für Biochemie (Prof. Galla)
Lischper, Mira
Institut für Biochemie
Zeni, Patrick
Institut für Biochemie