Disease relevance of SLPI

• Analysis of epithelial lining fluid samples from individuals with emphysema indicated the presence of cleaved SLPI in these samples whereas only intact SLPI was observed in control epithelial lining fluid samples [1].
• Our findings indicate that elafin and SLPI may be gene therapy targets for the treatment of atheroma [2].
• In the present study, we measured the concentrations of elafin, a newly described, low-molecular-weight serine proteinase inhibitor, SLPI, and alpha1(PI) in BAL fluids from eight healthy subjects, 13 asymptomatic farmers, seven farmers with active farmer's lung (FL), and seven farmers with previous (Ex) FL [3].
• Secretory leukocyte proteinase inhibitor (SLPI) is the main neutrophil elastase (HLE) inhibitor found in the upper airways during pulmonary inflammation [4].
• By logistic regression modeling, a salivary SLPI level exceeding 2.1 microg/ml, low CD4 count, antiretroviral monotherapy, and smoking were key predictors of oropharyngeal candidiasis [5].
• This study provides a new model for metastasis, based on the mechanism regulated by anti-invasive factors, such as SLPI [6].

Psychiatry related information on SLPI

• Timidity is modified statistically by showing an improved reading ability and through the measurement of extroversion on the MPI [7].
• The sample is assessed by the MPI (Maudsley Personality Inventory) and a rating scale [7].
• In conclusion, ALP-detected focal brain atrophy was strongly associated with dementia [8].
• The group of women with an eating disorder had significantly higher concentrations of total CO2, calcium, AST, ALT, ALP, albumin and cholesterol and significantly lower concentrations of potassium, chloride and phosphate in the plasma [9].
• MMPI and MPI could not separate TM and non-typus melancholicus (NTM) in univariate analyses [10].

High impact information on SLPI

• Increased leukocyte elastase activity in mice lacking secretory leukocyte protease inhibitor (SLPI) leads to impaired wound healing due to enhanced activity of TGFbeta and perhaps additional mechanisms [11].
• Supplying PEPI corrects the wound-healing defect in SLPI null mice [11].
• Thus, SLPI/elastase act via PEPI/EPIs to operate a switch at the interface between innate immunity and wound healing [11].
• These data demonstrate that MGDF is a novel cytokine that regulates megakaryocyte development and is a ligand for the MPI receptor [12].
• On examining 18 members of the "Clb2 cluster" of cell cycle-regulated proteins to which Hst3 belongs, we find that two others, Ynl058c and Alk1, are significantly downregulated on DNA damage [13].

Chemical compound and disease context of SLPI

• The aim of the present study was to determine the effect of apocynin on the efficacy of SLPI in preventing experimental emphysema [14].
• In addition to its antiprotease activity, SLPI has been shown to exhibit antiinflammatory properties, including down-regulation of tumor necrosis factor alpha expression by lipopolysaccharide (LPS) in macrophages and inhibition of nuclear factor (NF)-kappaB activation in a rat model of acute lung injury [15].
• Moreover, this HIV-1 PS interaction with annexin II can be disrupted by SLPI or other annexin II-specific inhibitors [16].
• SLPI-expressing carcinomas were reduced in number by transduction of the SLPI-directed toxin plasmid plus ganciclovir, but the same treatment had no effect on a cell line that did not express SLPI [17].
• Since chymase is considered to participate in mast-cell degranulation and histamine release, SLPI might act as a regulator of allergic reactions [18].

Biological context of SLPI

• However, SLPI is released upon platelet activation, which also reverses its association with the resting marginal band [19].
• SLPI(-/-) mice show intact proplatelet formation, platelet numbers and shape, and marginal MT bands; thus, SLPI is not essential for thrombopoiesis [19].
• The proteolytic cleavage of SLPI by all three cathepsins resulted in the loss of the active site of SLPI and the inactivation of SLPI anti-neutrophil elastase capacity [1].
• In contrast LZ and SLPI gene expression were reproducibly increased [20].
• Forced expression of BTEB1, either by stable or transient transfections of BTEB1 expression constructs in endometrial carcinoma cells, enhanced SLPI promoter activity [21].

Anatomical context of SLPI

• We conclude that SLPI localizes in part along the MK and platelet MT cytoskeleton by virtue of specific interactions with beta1 tubulin [19].
• Epithelial lining fluid (ELF) from patients suffering from BOS showed significantly increased neutrophil counts, significantly elevated concentrations of NE-API complex and Met(O), and a significant decrease in the concentration of SLPI [22].
• These results were compared with the chemoattractants interleukin-8 (IL-8) and leukotriene B(4) (LTB(4)), the bronchial inhibitor secretory leukoprotease inhibitor (SLPI), and protein leak (sputum/serum albumin ratio) [23].
• In the present study, we show that NCI-H322 cells produced higher amounts of both inhibitors than A549 cells and that basal production of SLPI in both cell lines is higher than the production of elafin/pre-elafin [24].
• Elafin stained predominantly in the epithelium and SLPI in mucosal inflammatory cells [25].

Associations of SLPI with chemical compounds

• We isolated secretory leukocyte protease inhibitor (SLPI), a serine protease antagonist characterized principally as a secreted factor with multiple roles in inflammation [19].
• Secretory leucoprotease inhibitor (SLPI) is an anti-inflammatory antiprotease which can inhibit lipopolysaccharide-induced NF-kappaB activation [26].
• Dexamethasone did not affect SLPI protein release from control or defensin-treated PBECs [27].
• Progesterone also acts in synergy with the proinflammatory cytokines, IL-1beta and TNFalpha, to increase SLPI [28].
• Progesterone treatment increases expression of SLPI mRNA and protein in the T47D breast epithelial cell line and this upregulation is attenuated in the presence of the anti-gestogens, RU486 and ZK98734, confirming the involvement of the nuclear progesterone receptor [28].
• A two-pronged approach confirmed that SLPI overcomes paclitaxel in part through activation of ERK1/2 [29].

Physical interactions of SLPI

• Noncovalent complexes between HLE and either the tight-binding secretory leucoprotease inhibitor (SLPI) or a slow tight-binding peptide difluoroketone inhibitor were not observed by ESI-MS [30].
• ALP bound to the actin-bundling protein L-plastin and down-modulated filamentous actin assembly in response to stimulation with IgG-coated latex beads in granulocytes [31].
• The activated glucocorticoid receptor translocates into the nucleus and binds to specific response elements in the promoter regions of anti-inflammatory genes such as lipocortin-1 and secretory leukocyte protease inhibitor (SLPI) [32].
• Secretory leukocyte protease inhibitor binds to annexin II, a cofactor for macrophage HIV-1 infection [16].

Enzymatic interactions of SLPI

• DNA-binding sites on HLE also participate in the upregulation of oxidized SLPI activity [33].
• Inhibition of neutrophil cathepsin G by oxidized mucus proteinase inhibitor. Effect of heparin [34].

Regulatory relationships of SLPI

• Furthermore, glucocorticoids were shown to increase both constitutive and NE-induced SLPI mRNA levels [27].
• We found that recombinant human SLPI in vitro inhibits TNF-alpha-induced hydrogen peroxide production by human neutrophils (ID50 = 1-2 microg/mL) [35].
• Cellular SLPI levels negatively influenced the anti-proliferative and pro-apoptotic insulin-like growth factor-binding protein-3 expression [36].
• In contrast, human skin fibroblasts exerted no SLPI-stimulated increase in HGF production, despite the fact that IL-1beta increased HGF production with an intensity similar to that of human lung fibroblasts [37].
• Leukocyte SLPI expression seems to be up-regulated in active WG [38].

Other interactions of SLPI

• Release of IL-10 by cervical explants and SLPI by peripheral blood and U937 cells were below the detection limit of the assays employed [39].
• Active cathepsin L was shown to be present in emphysema epithelial lining fluid and inhibition of this protease prevented the cleavage of recombinant SLPI added to emphysema epithelial lining fluid [1].
• Secretory leukocyte protease inhibitor (SLPI) and elafin are structurally similar, low-molecular-weight antiproteases produced in the lung [40].
• Western blot analysis showed the majority of alpha 1AT and SLPI molecules to be complexed and/or degraded [41].
• Elastase activity correlated with IL-8 (r = 0.55, p < 0.001) and LTB(4) (r = 0.41, p < 0.001) but negatively with SLPI (r = -0.49, p < 0.001) [23].

Analytical, diagnostic and therapeutic context of SLPI

• Measurements of SLPI in the lavage fluid samples by enzyme-linked immunosorbent assay (ELISA) agreed closely with values obtained by measuring the activity of this inhibitor [40].
• Immunohistochemistry using an anti-SLPI polyclonal antibody revealed positive staining of epithelial cells in the Fallopian tube [42].
• RT-PCR demonstrated that SLPI transcripts were expressed in the Fallopian tube [42].
• NE and SLPI amniotic fluid levels were determined by highly specific and sensitive immunoassays [43].
• SLPI mRNA expression was examined by Northern blotting, and SLPI promoter activity was measured using a reporter gene assay [44].

References