Alternative titles; symbols
HGNC Approved Gene Symbol: PI3
Cytogenetic location: 20q13.12 Genomic coordinates (GRCh38): 20:45,174,902-45,176,544 (from NCBI)
PI3 is a serine protease inhibitor that plays a major role as an antiinflammatory mediator at mucosal surfaces. In addition, PI3 has antibacterial activity against gram-positive and gram-negative bacterial and fungal pathogens (summary by Ghosh et al., 2009).
Chang et al. (1990) and Schalkwijk et al. (1990, 1991) described a low molecular weight elastase inhibitor derived from psoriatic skin and termed SKALP for 'skin-derived antileukoproteinase.' They demonstrated that this inhibitor can be found in the epidermis of several inflammatory skin diseases, but not in normal human epidermis. Wiedow et al. (1990) referred to this molecule as elafin, and Sallenave and Ryle (1991) referred to it as elastase-specific inhibitor. It is found in the urine of psoriatic patients, and immunohistochemical studies showed that SKALP/elafin is found in the suprabasal differentiated keratinocytes of psoriatic epidermis. Molhuizen et al. (1993) isolated a precursor of SKALP/elafin from cultured keratinocytes and cloned its cDNA.
Elafin is an antiproteinase and antimicrobial molecule that is expressed at epithelial sites (for example, cervix) (Sallenave, 2000). King et al. (2003) studied the expression and regulation of elafin in human endometrium. Real-time quantitative PCR showed that expression of elafin mRNA peaked during menstruation. Elafin protein was localized to leukocytes scattered in the endometrial stroma during the late secretory and menstrual phases. The authors concluded that endometrium expresses elafin in a menstruation-dependent manner.
Using RT-PCR and ELISA, Ghosh et al. (2009) detected elafin production in the female reproductive tract. Elafin production was enhanced following poly (I:C) stimulation. Recombinant elafin inhibited both lymphotropic and macrophage-tropic human immunodeficiency virus (HIV)-1 strains in a dose-dependent manner, possibly through direct interaction with the virus. Secreted elafin levels were higher, although not significantly, in cervico-vaginal lavages of HIV-1-negative women compared with HIV-1-positive women, and they were also higher in the secretory phase of the menstrual cycle compared with the proliferative phase. Ghosh et al. (2009) proposed that elafin may be an important endogenous microbicide in the female reproductive tract that is protective against HIV-1.
Molhuizen et al. (1994) localized the PI3 gene to chromosome 20 by study of somatic cell hybrids and to 20q12-q13 by in situ hybridization.
Kuijpers et al. (1998) could find no allelic association between pustular psoriasis, or psoriasis in general (see 177900), and polymorphism of the PI3 gene. The study was prompted by the finding of a decrease of SKALP, at the protein level, in lesional skin of patients with pustular psoriasis compared with plaque-type psoriasis.
Chang, A., Schalkwijk, J., Happle, R., van de Kerkhof, P. C. M. Elastase-inhibiting activity in scaling skin disorders. Acta Derm. Venerol. 70: 147-151, 1990. [PubMed: 1969201]
Ghosh, M., Shen, Z., Fahey, J. V., Cu-Uvin, S., Mayer, K., Wira, C. R. Trappin-2/Elafin: a novel innate anti-human immunodeficiency virus-1 molecule of the human female reproductive tract. Immunology 129: 207-219, 2009. [PubMed: 19824918] [Full Text: https://doi.org/10.1111/j.1365-2567.2009.03165.x]
King, A. E., Critchley, H. O. D., Sallenave, J.-M., Kelly, R. W. Elafin in human endometrium: an antiprotease and antimicrobial molecule expressed during menstruation. J. Clin. Endocr. Metab. 88: 4426-4431, 2003. [PubMed: 12970320] [Full Text: https://doi.org/10.1210/jc.2003-030239]
Kuijpers, A. L. A., Pfundt, R., Zeeuwen, P. L. J. M., Molhuizen, H. O. F., Mariman, E. C. M., van de Kerkhof, P. C. M., Schalkwijk, J. SKALP/elafin gene polymorphisms are not associated with pustular forms of psoriasis. Clin. Genet. 54: 96-101, 1998. [PubMed: 9727750] [Full Text: https://doi.org/10.1111/j.1399-0004.1998.tb03703.x]
Molhuizen, H. O. F., Alkemade, H. A. C., Zeeuwen, P. L. J. M., de Jongh, G. J., Wieringa, B., Schalkwijk, J. SKALP/elafin: an elastase inhibitor from cultured human keratinocytes: purification, cDNA sequence, and evidence for transglutaminase cross-linking. J. Biol. Chem. 268: 12028-12032, 1993. [PubMed: 7685029]
Molhuizen, H. O. F., Zeeuwen, P. L. J. M., Olde Weghuis, D., Geurts van Kessel, A., Schalkwijk, J. Assignment of the human gene encoding the epidermal serine proteinase inhibitor SKALP (PI3) to chromosome region 20q12-q13. Cytogenet. Cell Genet. 66: 129-131, 1994. [PubMed: 8287685] [Full Text: https://doi.org/10.1159/000133683]
Sallenave, J.-M., Ryle, A. P. Purification and characterization of elastase-specific inhibitor: sequence homology with mucus proteinase inhibitor. Biol. Chem. Hoppe Seyler 372: 13-21, 1991. [PubMed: 2039600] [Full Text: https://doi.org/10.1515/bchm3.1991.372.1.13]
Sallenave, J.-M. The role of secretory leukocyte proteinase inhibitor and elafin (elastase-specific inhibitor/skin-derived antileukoprotease) as alarm antiproteinases in inflammatory lung disease. Respir. Res. 1: 87-92, 2000. [PubMed: 11667971] [Full Text: https://doi.org/10.1186/rr18]
Schalkwijk, J., Chang, A., Janssen, P., de Jongh, G. J., Mier, P. D. Skin-derived antileucoproteases (SKALPs): characterization of two new elastase inhibitors from psoriatic epidermis. Brit. J. Derm. 122: 631-641, 1990. [PubMed: 2354116] [Full Text: https://doi.org/10.1111/j.1365-2133.1990.tb07285.x]
Schalkwijk, J., de Roo, C., de Jongh, G. J. Skin-derived antileukoproteinase (SKALP), an elastase inhibitor from human keratinocytes: purification and biochemical properties. Biochim. Biophys. Acta 1096: 148-154, 1991. [PubMed: 2001428] [Full Text: https://doi.org/10.1016/0925-4439(91)90053-c]
Wiedow, O., Schroder, J.-M., Gregory, H., Young, J. A., Christophers, E. Elafin: an elastase-specific inhibitor of human skin: purification, characterization, and complete amino acid sequence. J. Biol. Chem. 265: 14791-14795, 1990. Note: Erratum: J. Biol. Chem. 266: 3356 only, 1991. [PubMed: 2394696]