2024年8月22日 · We demonstrate that a CatC inhibitor, MOD06051, dose-dependently suppresses the cellular activity of NSPs, including neutrophil elastase (NE), in vitro. Neutrophils derived from...

Cathepsin C (CatC) from zymogens activates the proteolytic function of NSPs, including PR3. Lack of NSP zymogen activation results in neutrophils with strongly reduced NSP proteins.

2021年12月1日 · The authors argue that the tumor CatC-mediated activation of PR3 mb resulted in IL-1β processing and NFκb activation in the neutrophils. In the proposed scheme, this activation leads to the secretion of IL-6 and CCL3 further enhancing neutrophil recruitment to …

Results: BI 1291583 bound human CatC in a covalent, reversible manner, selectively and fully inhibiting CatC enzymatic activity. This inhibition translated to concentration-dependent inhibition of NE activation in U937 cells and dose-dependent, almost-complete inhibition of NE and PR3 activity in BALF neutrophils in an in vivo LPS-challenge ...

We explored CatC as a potential AAV treatment target to downregulate NSPs, including the PR3 autoantigen that drives PR3-AAV. Our study revealed several new findings. First, human CatC gene-deficiency in patients with PLS strongly reduced NSPs in both neutrophils and monocytes resulting in less neutrophil-mediated EC damage.

2024年11月1日 · This CatC-like protease(s), now called NSPs-Alternative Activating Protease-1 (NSPs-AAP-1), was capable of activating 80 % of PR3 and CatG when proCatC maturation was almost totally inhibited. We then investigated whether we could inhibit NSPs-AAP-1 using chemical inhibitors targeting CatC, by analyzing NSP activation in HL-60 cells.

2018年8月8日 · PR3 and related proteases are activated from pro-forms by the lysosomal cysteine protease cathepsin C (CatC) during neutrophil maturation. We hypothesized that pharmacological inhibition of CatC provides an effective measure to reduce PR3 m and therefore has implications as a novel therapeutic approach in granulomatosis with polyangiitis.

2024年1月1日 · In vitro, the exogenous addition of PR3 to CatC-deficient monocytes restored IL-1β production, suggesting that in vivo, anti MPO-induced NCGN is NSP-dependent. In GPA, PR3 constitutes the main target of ANCA.

2018年4月1日 · PR3 and related neutrophil serine proteases (NSP) are activated from proforms by the lysosomal cysteine protease cathepsin C (CatC) during neutrophil maturation. We hypothesized that pharmacological inhibition of CatC provides an effective measure to reduce intracellular and membrane-bound PR3 and has therefore implications as a novel ...

2018年8月10日 · PR3 and related proteases are activated from pro-forms by the lysosomal cysteine protease cathepsin C (CatC) during neutrophil maturation. We hypothesized that pharmacological inhibition of CatC provides an effective measure to reduce PR3 m and therefore has implications as a novel therapeutic approach in granulomatosis with polyangiitis.