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Elafin in Human Endometrium: An Antiprotease and Antimicrobial Molecule Expressed during Menstruation

Medical Research Council Human Reproductive Sciences Unit (A.E.K., R.W.K.) and Department of Reproductive and Developmental Sciences (H.O.D.C.), University of Edinburgh, Centre for Reproductive Biology, Edinburgh, United Kingdom EH16 4SB; and Centre for Inflammation Research (J.-M.S.), Edinburgh University Medical School, Edinburgh, United Kingdom EH8 9AG

Address all correspondence and requests for reprints to: Dr. Anne King, Medical Research Council Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Chancellor’s Building, 49 Little France Crescent, Edinburgh, United Kingdom EH16 4SB. E-mail: a.king{at}hrsu.mrc.ac.uk.

Elafin is an antiproteinase and antimicrobial molecule that is expressed at epithelial sites (for example, cervix). This study details the expression and regulation of elafin in the human endometrium. Elafin mRNA and protein expression were examined in endometrium throughout the menstrual cycle and in first-trimester decidua. 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. Faint immunostaining was also present in glandular epithelium at these cycle stages. Immunofluorescent colocalization of elafin with neutrophil elastase confirmed that elafin was expressed by endometrial neutrophils around the time of menstruation. This is consistent with the expression profile observed from immunohistochemical studies. Primary endometrial epithelial cells were treated with proinflammatory molecules, and elafin mRNA was studied. A combination of the proinflammatory mediators, IL-1ß and TNF, increased elafin mRNA levels by 4.6-fold. These results show that endometrium expresses elafin in a menstruation-dependent manner. This is attributable to the presence of infiltrating leukocytes and increased inflammatory signaling. Elafin will regulate proteolytic enzymes during menstruation and will contribute to the innate defense against uterine infection.

Abbreviations: MIgG, Mouse IgG; MMP, matrix metalloproteinase; NGS, normal goat serum; RIgG, rabbit IgG; SLPI, secretory leukocyte protease inhibitor; TIMP, tissue inhibitor of MMP.

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