Fig. 5
From: Candidalysin activates innate epithelial immune responses via epidermal growth factor receptor
MMP inhibition suppresses the candidalysin and C. albicans-induced response pathway. Pre-treatment of TR146 cells with Marimastat (MMP inhibitor, 10 µM) but not GI-253023X (ADAM10 inhibitor, 5 µM), significantly suppressed candidalysin-induced expression of pEGFR (Y1068 and Y845), c-Fos and pMKP1 (a). MMP inhibition had no suppressive effects on candidalysin-induced EREG (b) EPG (c), IL-1α (d), IL-1β (e) or IL-6 (f) but did suppress GM-CSF (g) and G-CSF (h) cytokine release. In Marimastat-inhibited, WT C. albicans-infected cells, significant suppression of all investigated proteins (i–o) except IL-6 (p), was observed. The candidalysin-deficient ece1Δ/Δ+ECE1Δ184–279 strain also failed to induce phosphorylation of EGFR or MKP1, c-Fos expression (i) or our panel of cytokines (l–p). Protein lysates were taken at 2 h post infection for western blot analysis, cytokines assessed at 24 h post infection via luminex. Solid vertical lines indicate omitted, extraneous portions of blot images. Unmatched, one-way ANOVA with Bonferroni multiple comparison’s test used to assess statistical significance. All images and graphs are representative of three independent experiments. One-way ANOVA with Bonferroni multiple comparison’s test was used to assess statistical significance. Error bars represent SD. *p < 0.05, **p < 0.01, ***p < 0.001
