title: The role of toll-like receptors 2 and 4 in the pathogenesis of feline pyometra.
abstract: Pyometra is the most common uterine disease in queens. To protect itself from infection, the female reproductive tract possesses several immune mechanisms that are based on germline-encoded pattern recognition receptors (toll-like receptors [TLRs]). The aim of our study was to examine endometrial immunolocalization of TLR2/4, study the influence of lipopolysaccharide (LPS) and tumor necrosis factor (TNF) α on messenger RNA expression of both receptors in pyometric queens, and compare these patterns between estrous cycling queens and those hormonally treated with medroxyprogesterone acetate (MPA). Thirty-six queens, ranging in age from 7 months to 11 years, were allocated into seven groups (anestrus, estrus, mid-diestrus and late diestrus, short-term and long-term hormonally treated queens, and pyometric queens). At the messenger RNA level, the real-time polymerase chain reaction was applied, whereas at the TLR2/4 protein level, the expression was tested by immunohistochemistry. In queens at estrus, gene expression of TLR2 was upregulated after stimulation of endometrial explants by TNF (P < 0.001) and by TNF together with the LPS (P < 0.01). Moreover, gene expression of TLR2 was significantly upregulated after stimulation by TNF (P < 0.001) and LPS (P < 0.01) explants derived from queens that had been long-term hormonally treated with MPA. Endometrial gene expression of TLR4 was significantly upregulated after incubation of explants with TNF (P < 0.001) in queens at estrus and with LPS (P < 0.05) in queens short-term hormonally treated with MPA. Immunolocalization reported that TLR2/4 receptors are mainly localized in the surface and glandular epithelia. These data show that short-term and especially long-term administration of progesterone derivatives impairs TLRs in the endometrial epithelium, presumably enabling pathogens to break through this first natural barrier and thereby increase the risk of pyometra development.
authors.affiliation: Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Jursza
authors.affiliation: Institute of Veterinary Anatomy, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
authors.forename: M P
authors.initials: MP
authors.lastname: Kowalewski
authors.affiliation: Institute of Veterinary Anatomy, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Boos
authors.affiliation: Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.
authors.forename: D J
authors.initials: DJ
authors.lastname: Skarzynski
authors.affiliation: Department of Animal Reproduction with Clinic, Faculty of Veterinary Medicine, University of Warmia and Mazury, Olsztyn, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Socha
authors.affiliation: Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland. Electronic address: m.siemieniuch@pan.olsztyn.pl.
authors.forename: M J
authors.initials: MJ
authors.lastname: Siemieniuch
mesh_terms: D000818:Animals; D002371:Cat Diseases / Q000209:etiology / Q000378:metabolism*; D002415:Cats; D003271:Contraceptive Agents, Female / Q000494:pharmacology; D030762:Estrous Cycle; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D055112:Pyometra / Q000209:etiology / Q000378:metabolism / Q000662:veterinary*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D003271:Contraceptive Agents, Female; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D017258:Medroxyprogesterone Acetate
keywords: Cat; Endometrium; Pyometra; Toll-like receptor 2/4