Fig. 10: Psoriatic skin eluates contain IL-36β-processing activity that can be suppressed by cathepsin G-targeted pseudosubstrates.

a HeLa^IL-36R-SEAP cells were stimulated with skin eluates from either healthy volunteer controls, or eluates from uninvolved (non-lesional) or involved (lesional) skin areas from psoriatic individuals (n = 6 per group). After 24 h, cytokine concentrations in the culture supernatants were determined by ELISA. b HeLa^IL-36R-SEAP cells were stimulated with skin eluates from lesional areas of psoriatic individuals (n = 6), either alone, or after incubation of the same eluates for 2 h at 37 °C with recombinant IL36α, -β, or -γ (500 pM). After 24 h, cytokine concentrations in the culture supernatants were determined by ELISA. c HeLa^IL-36R-SEAP cells were stimulated with IL36β (500 pM) that had been pre-incubated for 2 h at 37 °C with skin eluates from lesional areas of psoriatic individuals (n = 6), either alone (blue symbols), or in combination with the indicated concentrations of the novel cathepsin G (z-EPF-cmk) or cathepsin G/elastase (z-EPF-API-cmk) peptide inhibitors (maroon symbols). Cathepsin G Inhibitor I (Merck) served as a positive control and the elastase inhibitor (z-API-cmk) as a negative control (bottom panels). After 24 h, cytokine concentrations in the culture supernatants were determined by ELISA. Results shown are representative of at least three independent experiments