Disease relevance of Serpinb9

• Spi6 KO mice in turn were impaired in their ability to clear LCMV infection [1].
• In mouse models, both elevated expression of Spi6 and the complete absence of granzyme B in CD8+ T cells led to an increase in memory cells after infection with lymphocytic choriomeningitis virus [2].
• In light of prior studies indicating that virally infected hepatocytes are selectively resistant to this CTL effector mechanism, the present studies investigated PI-9 and SPI-6 expression in hepatocytes and hepatoma cells in response to adenoviral infection and to cytokines produced during antiviral immune responses [3].

High impact information on Serpinb9

• We conclude that Spi6 protects CTLs from suicide caused by GrB-mediated breakdown of cytotoxic granules [1].
• We propose that expression of protective molecules, like Spi6, serves to shield metabolically active CD8+ memory T cells from their own effector molecules [2].
• These findings indicate that cytokines that promote antiviral cytopathic responses also regulate expression of the cytoprotective molecules, PI-9 and SPI-6, in hepatocytes that are potential targets of CTL and NK effector mechanisms [3].
• By RNA analysis only one of the two sequences resembling PI-9 (designated SPI6) is present in mouse lymphocytes while the other (a partial clone designated mBM2A) is predominantly in testis [4].
• In a search for the murine equivalent of PI-9 we screened cDNA libraries, and performed reverse transcriptase-polymerase chain reaction on RNA isolated from leukocyte cell lines and from lymph nodes and spleens of allo-immunized mice [4].

Biological context of Serpinb9

• Serine protease inhibitor 6 (SPI-6), also called Serpinb9, inhibits granzyme B and thus may provide a method for delaying apoptotic cell death in dendritic cells [5].
• Our identification of multiple sequence homologs of PI-8 and PI-9, and six new ovalbumin serpins, is consonant with the idea that the larger set of granule and other proteinases known to exist in the mouse (compared with human) is balanced by a larger array of serpins [4].
• 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 [6].
• Knockdown of PI-9 by RNA interference blocked the protective effect of estrogen [6].
• Nucleotide sequences of the clones revealed that one clone, cap3, contained an open reading frame (ORF) that would code for a 26-amino acid, cysteine-rich peptide with significant homology to Neurospora crassa copper metallothionein [7].

Anatomical context of Serpinb9

• Here, we show by immunohistochemistry that PI-9 is also abundantly expressed in human testicular Sertoli cells and placental syncytial trophoblasts [8].
• We report here the cloning of 3 new CAP isoforms, CAP2, CAP3, and CAP4, from mouse adipose tissue [9].

Analytical, diagnostic and therapeutic context of Serpinb9

• Neither PI-9 nor SPI-6 expression was detected by immunoblotting in uninfected murine or human hepatocytes [3].

References