Povzetek
Cystatin F is a protein inhibitor of cysteine cathepsins, peptidases involved in the activation of the effector molecules of the perforin/granzyme pathway. Cystatin F was previously shown to regulate natural killer cell cytotoxicity. Here, we show that extracellular cystatin F has a role in regulating the killing efficiency of cytotoxic T lymphocytes (CTLs). Extracellular cystatin F was internalised into TALL-104 cells, a cytotoxic T cell line, and decreased their cathepsin C and H activity. Correspondingly, granzyme A and B activity was also decreased and, most importantly, the killing efficiency of TALL-104 cells as well as primary human CTLs was reduced. The N-terminally truncated form of cystatin F, which can directly inhibit cathepsin C (unlike the full-length form), was more effective than the full-length inhibitor. Furthermore, cystatin F decreased cathepsin L activity, which, however, did not affect perforin processing. Cystatin F derived from K-562 target cells could also decrease the cytotoxicity of TALL-104 cells. These results clearly show that, by inhibiting cysteine cathepsin proteolytic activity, extracellular cystatin F can decrease the cytotoxicity of CTLs and thus compromise their function.
Ključne besede
cystatin F;cathepsins;cytotoxic lymphocytes;
Podatki
Jezik: |
Angleški jezik |
Leto izida: |
2020 |
Tipologija: |
1.01 - Izvirni znanstveni članek |
Organizacija: |
UL FFA - Fakulteta za farmacijo |
UDK: |
616.1 |
COBISS: |
43955203
|
ISSN: |
2072-6694 |
Št. ogledov: |
156 |
Št. prenosov: |
44 |
Ocena: |
0 (0 glasov) |
Metapodatki: |
|
Ostali podatki
Sekundarni jezik: |
Slovenski jezik |
Sekundarne ključne besede: |
cistatin F;katepsini;citotoksični limfociti; |
Vrsta dela (COBISS): |
Članek v reviji |
Strani: |
str. 1-14 |
Letnik: |
ǂVol. ǂ12 |
Zvezek: |
ǂiss. ǂ12 |
Čas izdaje: |
Dec. 2020 |
DOI: |
10.3390/cancers12123660 |
ID: |
14452185 |