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Gene Review

SLPI  -  secretory leukocyte peptidase inhibitor

Homo sapiens

Synonyms: ALK1, ALP, Antileukoproteinase, BLPI, HUSI, ...
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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


Biological context of SLPI


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


Enzymatic interactions of SLPI


Regulatory relationships of SLPI


Other interactions of SLPI


Analytical, diagnostic and therapeutic context of SLPI


  1. Cathepsin B, L, and S cleave and inactivate secretory leucoprotease inhibitor. Taggart, C.C., Lowe, G.J., Greene, C.M., Mulgrew, A.T., O'Neill, S.J., Levine, R.L., McElvaney, N.G. J. Biol. Chem. (2001) [Pubmed]
  2. Adenoviral gene delivery of elafin and secretory leukocyte protease inhibitor attenuates NF-kappa B-dependent inflammatory responses of human endothelial cells and macrophages to atherogenic stimuli. Henriksen, P.A., Hitt, M., Xing, Z., Wang, J., Haslett, C., Riemersma, R.A., Webb, D.J., Kotelevtsev, Y.V., Sallenave, J.M. J. Immunol. (2004) [Pubmed]
  3. Elafin/elastase-specific inhibitor in bronchoalveolar lavage of normal subjects and farmer's lung. Tremblay, G.M., Sallenave, J.M., Israél-Assayag, E., Cormier, Y., Gauldie, J. Am. J. Respir. Crit. Care Med. (1996) [Pubmed]
  4. Secretory leukocyte proteinase inhibitor is a major leukocyte elastase inhibitor in human neutrophils. Sallenave, J.M., Si Tahar, M., Cox, G., Chignard, M., Gauldie, J. J. Leukoc. Biol. (1997) [Pubmed]
  5. Salivary secretory leukocyte protease inhibitor and oral candidiasis in human immunodeficiency virus type 1-infected persons. Chattopadhyay, A., Gray, L.R., Patton, L.L., Caplan, D.J., Slade, G.D., Tien, H.C., Shugars, D.C. Infect. Immun. (2004) [Pubmed]
  6. The secretory leukocyte protease inhibitor (SLPI) suppresses cancer cell invasion but promotes blood-borne metastasis via an invasion-independent pathway. Sugino, T., Yamaguchi, T., Ogura, G., Kusakabe, T., Goodison, S., Homma, Y., Suzuki, T. J. Pathol. (2007) [Pubmed]
  7. The treatment of extreme shyness in maladjusted children by implosive, counselling and conditioning approaches. Lowenstein, L.F. Acta psychiatrica Scandinavica. (1982) [Pubmed]
  8. Morphometric analysis of gray matter volume in demented older adults: exploratory analysis of the cardiovascular health study brain MRI database. Rosano, C., Becker, J., Lopez, O., Lopez-Garcia, P., Carter, C.S., Newman, A., Kuller, L., Aizenstein, H. Neuroepidemiology. (2005) [Pubmed]
  9. Biochemical abnormalities in anorexia nervosa and bulimia. Mira, M., Stewart, P.M., Vizzard, J., Abraham, S. Ann. Clin. Biochem. (1987) [Pubmed]
  10. Personality and endogenous/major depression: an empirical approach to typus melancholicus. 2. Validation of typus melancholicus core-properties by personality inventory scales. Mundt, C., Backenstrass, M., Kronmiller, K.T., Fiedler, P., Kraus, A., Stanghellini, G. Psychopathology. (1997) [Pubmed]
  11. Conversion of proepithelin to epithelins: roles of SLPI and elastase in host defense and wound repair. Zhu, J., Nathan, C., Jin, W., Sim, D., Ashcroft, G.S., Wahl, S.M., Lacomis, L., Erdjument-Bromage, H., Tempst, P., Wright, C.D., Ding, A. Cell (2002) [Pubmed]
  12. Identification and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine receptor Mpl. Bartley, T.D., Bogenberger, J., Hunt, P., Li, Y.S., Lu, H.S., Martin, F., Chang, M.S., Samal, B., Nichol, J.L., Swift, S. Cell (1994) [Pubmed]
  13. Cell cycle and checkpoint regulation of histone H3 K56 acetylation by Hst3 and Hst4. Maas, N.L., Miller, K.M., DeFazio, L.G., Toczyski, D.P. Mol. Cell (2006) [Pubmed]
  14. Apocynin improves the efficacy of secretory leukocyte protease inhibitor in experimental emphysema. Stolk, J., Rossie, W., Dijkman, J.H. Am. J. Respir. Crit. Care Med. (1994) [Pubmed]
  15. Secretory leucoprotease inhibitor binds to NF-kappaB binding sites in monocytes and inhibits p65 binding. Taggart, C.C., Cryan, S.A., Weldon, S., Gibbons, A., Greene, C.M., Kelly, E., Low, T.B., O'neill, S.J., McElvaney, N.G. J. Exp. Med. (2005) [Pubmed]
  16. Secretory leukocyte protease inhibitor binds to annexin II, a cofactor for macrophage HIV-1 infection. Ma, G., Greenwell-Wild, T., Lei, K., Jin, W., Swisher, J., Hardegen, N., Wild, C.T., Wahl, S.M. J. Exp. Med. (2004) [Pubmed]
  17. Strategy for achieving selective killing of carcinomas. Garver, R.I., Goldsmith, K.T., Rodu, B., Hu, P.C., Sorscher, E.J., Curiel, D.T. Gene Ther. (1994) [Pubmed]
  18. The effect of immediate-hypersensitivity reactions on the level of SLPI, granulocyte elastase, alpha1-antitrypsin, and albumin in nasal secretions, by the method of unilateral antigen challenge. Westin, U., Lundberg, E., Wihl, J.A., Ohlsson, K. Allergy (1999) [Pubmed]
  19. Interactions between the megakaryocyte/platelet-specific beta1 tubulin and the secretory leukocyte protease inhibitor SLPI suggest a role for regulated proteolysis in platelet functions. Schulze, H., Korpal, M., Bergmeier, W., Italiano, J.E., Wahl, S.M., Shivdasani, R.A. Blood (2004) [Pubmed]
  20. Regulation of the secretory phenotype of human airway epithelium by retinoic acid, triiodothyronine, and extracellular matrix. Yoon, J.H., Gray, T., Guzman, K., Koo, J.S., Nettesheim, P. Am. J. Respir. Cell Mol. Biol. (1997) [Pubmed]
  21. Progesterone receptor transactivation of the secretory leukocyte protease inhibitor gene in Ishikawa endometrial epithelial cells involves recruitment of Krüppel-like factor 9/basic transcription element binding protein-1. Velarde, M.C., Iruthayanathan, M., Eason, R.R., Zhang, D., Simmen, F.A., Simmen, R.C. Endocrinology (2006) [Pubmed]
  22. Bronchiolitis obliterans syndrome after (heart-)lung transplantation. Impaired antiprotease defense and increased oxidant activity. Hirsch, J., Elssner, A., Mazur, G., Maier, K.L., Bittmann, I., Behr, J., Schwaiblmair, M., Reichenspurner, H., Fürst, H., Briegel, J., Vogelmeier, C. Am. J. Respir. Crit. Care Med. (1999) [Pubmed]
  23. The interrelationship of sputum inflammatory markers in patients with chronic bronchitis. Hill, A.T., Bayley, D., Stockley, R.A. Am. J. Respir. Crit. Care Med. (1999) [Pubmed]
  24. Regulation of secretory leukocyte proteinase inhibitor (SLPI) and elastase-specific inhibitor (ESI/elafin) in human airway epithelial cells by cytokines and neutrophilic enzymes. Sallenave, J.M., Shulmann, J., Crossley, J., Jordana, M., Gauldie, J. Am. J. Respir. Cell Mol. Biol. (1994) [Pubmed]
  25. Attenuated induction of epithelial and leukocyte serine antiproteases elafin and secretory leukocyte protease inhibitor in Crohn's disease. Schmid, M., Fellermann, K., Fritz, P., Wiedow, O., Stange, E.F., Wehkamp, J. J. Leukoc. Biol. (2007) [Pubmed]
  26. Secretory leucoprotease inhibitor impairs Toll-like receptor 2- and 4-mediated responses in monocytic cells. Greene, C.M., McElvaney, N.G., O'Neill, S.J., Taggart, C.C. Infect. Immun. (2004) [Pubmed]
  27. Regulation of SLPI and elafin release from bronchial epithelial cells by neutrophil defensins. van Wetering, S., van der Linden, A.C., van Sterkenburg, M.A., de Boer, W.I., Kuijpers, A.L., Schalkwijk, J., Hiemstra, P.S. Am. J. Physiol. Lung Cell Mol. Physiol. (2000) [Pubmed]
  28. Differential regulation of secretory leukocyte protease inhibitor and elafin by progesterone. King, A.E., Morgan, K., Sallenave, J.M., Kelly, R.W. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  29. Secretory leukocyte protease inhibitor antagonizes paclitaxel in ovarian cancer cells. Rasool, N., LaRochelle, W., Zhong, H., Ara, G., Cohen, J., Kohn, E.C. Clin. Cancer Res. (2010) [Pubmed]
  30. Electrospray ionization mass spectrometry as a mechanistic tool: mass of human leucocyte elastase and a beta-lactam-derived E-I complex. Knight, W.B., Swiderek, K.M., Sakuma, T., Calaycay, J., Shively, J.E., Lee, T.D., Covey, T.R., Shushan, B., Green, B.G., Chabin, R. Biochemistry (1993) [Pubmed]
  31. Antileukoproteinase: modulation of neutrophil function and therapeutic effects on anti-type II collagen antibody-induced arthritis. Sehnert, B., Cavcic, A., Böhm, B., Kalden, J.R., Nandakumar, K.S., Holmdahl, R., Burkhardt, H. Arthritis Rheum. (2004) [Pubmed]
  32. Effects of glucocorticoids on gene transcription. Hayashi, R., Wada, H., Ito, K., Adcock, I.M. Eur. J. Pharmacol. (2004) [Pubmed]
  33. DNA from bronchial secretions modulates elastase inhibition by alpha(1)-proteinase inhibitor and oxidized secretory leukoprotease inhibitor. Ying, Q.L., Simon, S.R. Am. J. Respir. Cell Mol. Biol. (2000) [Pubmed]
  34. Inhibition of neutrophil cathepsin G by oxidized mucus proteinase inhibitor. Effect of heparin. Boudier, C., Cadène, M., Bieth, J.G. Biochemistry (1999) [Pubmed]
  35. Secretory leukocyte protease inhibitor, an inhibitor of neutrophil activation, is elevated in serum in human sepsis and experimental endotoxemia. Grobmyer, S.R., Barie, P.S., Nathan, C.F., Fuortes, M., Lin, E., Lowry, S.F., Wright, C.D., Weyant, M.J., Hydo, L., Reeves, F., Shiloh, M.U., Ding, A. Crit. Care Med. (2000) [Pubmed]
  36. Secretory leukocyte protease inhibitor mediates proliferation of human endometrial epithelial cells by positive and negative regulation of growth-associated genes. Zhang, D., Simmen, R.C., Michel, F.J., Zhao, G., Vale-Cruz, D., Simmen, F.A. J. Biol. Chem. (2002) [Pubmed]
  37. Secretory leukoprotease inhibitor augments hepatocyte growth factor production in human lung fibroblasts. Kikuchi, T., Abe, T., Yaekashiwa, M., Tominaga, Y., Mitsuhashi, H., Satoh, K., Nakamura, T., Nukiwa, T. Am. J. Respir. Cell Mol. Biol. (2000) [Pubmed]
  38. Increased expression of the secretory leukocyte proteinase inhibitor in Wegener's granulomatosis. Ohlsson, S., Falk, R., Yang, J.J., Ohlsson, K., Segelmark, M., Wieslander, J. Clin. Exp. Immunol. (2003) [Pubmed]
  39. Seminal plasma components stimulate interleukin-8 and interleukin-10 release. Denison, F.C., Grant, V.E., Calder, A.A., Kelly, R.W. Mol. Hum. Reprod. (1999) [Pubmed]
  40. Contribution of secretory leukocyte proteinase inhibitor to the antiprotease defense system of the peripheral lung: effect of ozone-induced acute inflammation. Nadziejko, C., Finkelstein, I., Balmes, J.R. Am. J. Respir. Crit. Care Med. (1995) [Pubmed]
  41. Protease-antiprotease imbalance in the lungs of children with cystic fibrosis. Birrer, P., McElvaney, N.G., Rüdeberg, A., Sommer, C.W., Liechti-Gallati, S., Kraemer, R., Hubbard, R., Crystal, R.G. Am. J. Respir. Crit. Care Med. (1994) [Pubmed]
  42. The expression of secretory leukocyte protease inhibitor (SLPI) in the fallopian tube: SLPI protects the acrosome reaction of sperm from inhibitory effects of elastase. Ota, Y., Shimoya, K., Zhang, Q., Moriyama, A., Chin, R., Tenma, K., Kimura, T., Koyama, M., Azuma, C., Murata, Y. Hum. Reprod. (2002) [Pubmed]
  43. Neutrophil elastase and secretory leukocyte protease inhibitor in prelabor rupture of membranes, parturition and intra-amniotic infection. Helmig, B.R., Romero, R., Espinoza, J., Chaiworapongsa, T., Bujold, E., Gomez, R., Ohlsson, K., Uldbjerg, N. J. Matern. Fetal. Neonatal. Med. (2002) [Pubmed]
  44. Adenoviral E1A suppresses secretory leukoprotease inhibitor and elafin secretion in human alveolar epithelial cells and bronchial epithelial cells. Higashimoto, Y., Yamagata, Y., Iwata, T., Ishiguchi, T., Okada, M., Masuda, M., Satoh, H., Itoh, H. Respiration; international review of thoracic diseases. (2005) [Pubmed]
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