Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protease inhibitors are major secretory components of the mammalian uterus that are thought to mediate pregnancy-associated events primarily by regulating the activity of proteolytic enzymes. In the present study, we examined the mitogenic potentials of two serine protease inhibitors, namely secretory leukocyte protease inhibitor (SLPI) and uterine plasmin/trypsin inhibitor (UPTI) in primary cultures of glandular epithelial (GE) cells isolated from early pregnant (Day 12) pig endometrium, using the [(3)H]thymidine incorporation assay. Purified porcine SLPI (pSPLI), porcine UPTI (pUPTI), or recombinant human SLPI (rhSLPI), all of which exhibited anti-trypsin activity, increased (p < 0.05) labeled thymidine incorporation into DNA of serum-deprived GE cells when tested at a range of 10-1000-ng/ml concentrations. Polyclonal antibodies directed against either hSLPI or pSLPI abrogated the effect of SLPI. Co-addition of pSLPI and pUPTI increased DNA synthesis in these cells to a level higher (p < 0.05) than that observed with either protease inhibitor. The glycosaminoglycan heparin, which has been previously shown to increase the anti-protease activity of SLPI, exhibited a tendency (p = 0.08) to enhance SLPI and UPTI induction of cellular DNA synthesis. Reverse transcription-polymerase chain reaction indicated that the messenger RNAs for both protease inhibitors were present in the endometrium throughout pregnancy and, within this tissue, in GE cells to a greater extent (p < 0.05) than in stromal fibroblastic cells. Results demonstrate that, in addition to their well-documented anti-protease activities, SLPI and UPTI may constitute autocrine growth promotants for the uterine epithelium. These data suggest a novel mechanism whereby locally produced protease inhibitors may modulate periimplantation events and embryo-maternal communication.
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PMID:Uterine-associated serine protease inhibitors stimulate deoxyribonucleic acid synthesis in porcine endometrial glandular epithelial cells of pregnancy. 1041 15

Differential expression of secretory leukocyte protease inhibitor (SLPI) impacts on tumor progression. SLPI directly inhibits elastase and other serine proteases, and regulates matrix metalloproteinases, plasminogen activation, and plasmin downstream targets to influence invasion. We examined tissues from human oral squamous cell carcinoma (OSCC) for SLPI expression in parallel with proteases associated with tumor progression and evaluated their relationships using tumor cell lines. Significantly decreased SLPI was detected in OSCC compared to normal oral epithelium. Furthermore, an inverse correlation between SLPI and histological parameters associated with tumor progression, including stage of invasion, pattern of invasion, invasive cell grade, and composite histological tumor score was evident. Conversely, elevated plasmin and elastase were positively correlated with histological parameters of tumor invasion. In addition to its known inhibition of elastase, we identify SLPI as a novel inhibitor of plasminogen activation through its interaction with annexin A2 with concomitant reduced plasmin generation by macrophages and OSCC cell lines. In an in vitro assay measuring invasive activity, SLPI blocked protease-dependent tumor cell migration. Our data suggest that SLPI may possess antitumorigenic activity by virtue of its ability to interfere with multiple requisite proteolytic steps underlying tumor cell invasion and may provide insight into potential stratification of oral cancer according to risk of occult metastasis, guiding treatment strategies.
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PMID:Secretory leukocyte protease inhibitor (SLPI) expression and tumor invasion in oral squamous cell carcinoma. 2164 6