Sepsis is a life-threatening condition caused by the dysregulated host response to
infection. Novel therapeutic options are urgently needed and
aquaporin inhibitors could suffice as
aquaporin 5 (Aqp5) knockdown provided enhanced
sepsis survival in a murine
sepsis model. Potential AQP5 inhibitors provide
sulfonamides and their derivatives. In this study, we tested the hypothesis that
sulfonamides reduce AQP5 expression in different conditions. The impact of
sulfonamides on AQP5 expression and immune cell migration was examined in cell lines REH and RAW 264.7 by qPCR, Western blot and migration assay. Subsequently, whether
furosemide and
methazolamide are capable of reducing AQP5 expression after LPS incubation was investigated in whole blood samples of healthy volunteers. Incubation with
methazolamide (10-5 M) and
furosemide (10-6 M) reduced AQP5
mRNA and
protein expression by about 30% in REH cells. Pre-incubation of the cells with
methazolamide reduced cell migration towards SDF1-α compared to non-preincubated cells to control level. Pre-incubation with
methazolamide in PBMCs led to a reduction in LPS-induced AQP5 expression compared to control levels, while
furosemide failed to reduce it.
Methazolamide appears to reduce AQP5 expression and migration of immune cells. However, after LPS administration, the reduction in AQP5 expression by
methazolamide is no longer possible. Hence, our study indicates that
methazolamide is capable of reducing AQP5 expression and has the potential to be used in
sepsis prophylaxis.