Dexamethasone prevents alteration of tight junction-associated proteins and barrier function in porcine choroid plexus epithelial cells after infection with Streptococcus suis in vitro.

Apart from antibiotic treatment in bacterial meningitis supportive therapy including dexamethasone is widely used. In investigations on the pathogenesis of bacterial meningitis we previously demonstrated that Streptococcus suis (S. suis), a relevant cause of bacterial meningitis in pigs and humans, affects porcine choroid plexus epithelial cell (PCPEC) barrier function. The choroid plexus epithelium constitutes the structural basis of the blood-CSF barrier. Now, we investigated the role of tight junction proteins and the actin cytoskeleton of PCPEC in correlation to barrier function after S. suis infection and analyzed the influence of dexamethasone. S. suis caused massive rearrangement of the tight junction proteins ZO-1, occludin and claudin-1, caused loss of actin at the apical cell pole and induced basolateral stress fiber formation. Moreover, tight junctions were shifted from the Triton X insoluble to the Triton X soluble fraction, and additionally occludin was dephosphorylated and degraded. Infection with S. suis leads to an inflammatory response exemplified by the induction of tumor necrosis factor (TNF) alpha and matrix metalloproteinase (MMP)-3 gene activation, which correlated with phosphorylation of extracellular signal regulated kinases (ERKs). Importantly, dexamethasone significantly prevented S.suis-induced protein and morphological tight junction alterations and attenuated ERK activation and MMP-3 expression. It especially improved the barrier function by preventing tight junction protein reorganization and degradation. In the pathogenesis of bacterial meningitis protection of blood-CSF barrier by dexamethasone may prevent the penetration of bacteria and leukocytes into the CSF.