Increased proteinase inhibitor-9 (PI-9) and reduced granzyme B in lung cancer: Mechanism for immune evasion?

Lung Cancer ◽  
2012 ◽  
Vol 77 (1) ◽  
pp. 38-45 ◽  
Author(s):  
Cyd Soriano ◽  
Violet Mukaro ◽  
Greg Hodge ◽  
Jessica Ahern ◽  
Mark Holmes ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Evasion ◽  
Proteinase Inhibitor ◽  
Granzyme B ◽  
Proteinase Inhibitor 9

scholarly journals Selective Regulation of Apoptosis: the Cytotoxic Lymphocyte Serpin Proteinase Inhibitor 9 Protects against Granzyme B-Mediated Apoptosis without Perturbing the Fas Cell Death Pathway

1998 ◽  
Vol 18 (11) ◽  
pp. 6387-6398 ◽  
Author(s):  
Catherina H. Bird ◽  
Vivien R. Sutton ◽  
Jiuru Sun ◽  
Claire E. Hirst ◽  
Andrea Novak ◽  
...  
Keyword(s):  
Proteinase Inhibitor ◽  
Granzyme B ◽  
Target Cells ◽  
Cytotoxic Lymphocytes ◽  
Caspase Inhibitor ◽  
Caspase Activation ◽  
Cytotoxic Lymphocyte ◽  
Transfected Cells ◽  
Cell Death Pathway ◽  
Proteinase Inhibitor 9

ABSTRACT Cytotoxic lymphocytes (CLs) induce caspase activation and apoptosis of target cells either through Fas activation or through release of granule cytotoxins, particularly granzyme B. CLs themselves resist granule-mediated apoptosis but are eventually cleared via Fas-mediated apoptosis. Here we show that the CL cytoplasmic serpin proteinase inhibitor 9 (PI-9) can protect transfected cells against apoptosis induced by either purified granzyme B and perforin or intact CLs. A PI-9 P1 mutant (Glu to Asp) is a 100-fold-less-efficient granzyme B inhibitor that no longer protects against granzyme B-mediated apoptosis. PI-9 is highly specific for granzyme B because it does not inhibit eight of the nine caspases tested or protect transfected cells against Fas-mediated apoptosis. In contrast, the P1(Asp) mutant is an effective caspase inhibitor that protects against Fas-mediated apoptosis. We propose that PI-9 shields CLs specifically against misdirected granzyme B to prevent autolysis or fratricide, but it does not interfere with homeostatic deletion via Fas-mediated apoptosis.

scholarly journals Estrogen Induction of the Granzyme B Inhibitor, Proteinase Inhibitor 9, Protects Cells against Apoptosis Mediated by Cytotoxic T Lymphocytes and Natural Killer Cells

Endocrinology ◽  
2006 ◽  
Vol 147 (3) ◽  
pp. 1419-1426 ◽  
Author(s):  
Xinguo Jiang ◽  
Brent A. Orr ◽  
David M. Kranz ◽  
David J. Shapiro
Keyword(s):  
T Lymphocytes ◽  
Natural Killer ◽  
Cytotoxic T Lymphocytes ◽  
Proteinase Inhibitor ◽  
Nk Cell ◽  
Granzyme B ◽  
Liver Cells ◽  
Target Cells ◽  
Proteinase Inhibitor 9 ◽  
Estrogen Induction

Exposure to estrogens is associated with an increased risk of developing breast, cervical, and liver cancer. Estrogens strongly induce the human granzyme B inhibitor, proteinase inhibitor 9 (PI-9). Because cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells use the granzyme pathway to induce apoptosis of target cells, we tested the ability of activated CTLs and the human NK cell line, YT cells, to lyse human liver cells. Estrogen induction of PI-9 protected the liver cells against CTL and NK cell-mediated, granzyme-dependent, apoptosis. Knockdown of PI-9 by RNA interference blocked the protective effect of estrogen. This work demonstrates that estrogens can act on target cells to control their destruction by immune system cells and shows that induction of PI-9 expression can inhibit both CTL and NK cell-mediated apoptosis. Estrogen induction of PI-9 may reduce the ability of cytolytic lymphocytes-mediated immune surveillance to destroy newly transformed cells, possibly providing a novel mechanism for an estrogen-mediated increase in tumor incidence.

Presence of proteinase inhibitor-9 and granzyme B in healthy and pathological human corneas

2016 ◽  
Vol 94 ◽  
Author(s):  
K. Jirsova ◽  
S. Reinstein Merjava ◽  
M. Chudickova ◽  
V. Holan
Keyword(s):  
Proteinase Inhibitor ◽  
Granzyme B ◽  
Proteinase Inhibitor 9

scholarly journals Antiviral Cytokines Induce Hepatic Expression of the Granzyme B Inhibitors, Proteinase Inhibitor 9 and Serine Proteinase Inhibitor 6

2004 ◽  
Vol 172 (10) ◽  
pp. 6453-6459 ◽  
Author(s):  
Mahmoud B. Barrie ◽  
Heather W. Stout ◽  
Marwan S. Abougergi ◽  
Bonnie C. Miller ◽  
Dwain L. Thiele
Keyword(s):  
Proteinase Inhibitor ◽  
Granzyme B ◽  
Serine Proteinase ◽  
Serine Proteinase Inhibitor ◽  
Hepatic Expression ◽  
Proteinase Inhibitor 9

Altered sputum granzyme B and granzyme B/proteinase inhibitor-9 in patients with non-eosinophilic asthma

Respirology ◽  
2013 ◽  
Vol 19 (2) ◽  
pp. 280-287 ◽  
Author(s):  
Jodie L Simpson ◽  
Peter G Gibson ◽  
Ian A Yang ◽  
John Upham ◽  
Alan James ◽  
...  
Keyword(s):  
Proteinase Inhibitor ◽  
Granzyme B ◽  
Eosinophilic Asthma ◽  
Proteinase Inhibitor 9

The granzyme B inhibitor proteinase inhibitor 9 (PI9) is expressed by human mast cells

2005 ◽  
Vol 35 (4) ◽  
pp. 1175-1183 ◽  
Author(s):  
Bellinda?A. Bladergroen ◽  
Merel?C.?M. Strik ◽  
Angela?M. Wolbink ◽  
Dorine Wouters ◽  
Roel Broekhuizen ◽  
...  
Keyword(s):  
Mast Cells ◽  
Proteinase Inhibitor ◽  
Granzyme B ◽  
Human Mast Cells ◽  
Proteinase Inhibitor 9
Sign in / Sign up

Export Citation Format

Share Document