Expression and subcellular localization of TLR-4 in term and first trimester human placenta |
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| Authors: | Beijar E C E Mallard C Powell T L |
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| Affiliation: | 1. Graduate Program in Microbiology and Immunology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA;2. Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA;3. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA;4. Center for Quantitative Sciences, Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, 37232, USA;5. Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA;6. Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA;7. Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, NE, 68198, USA;8. Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA;9. Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA;1. Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Norway;2. Division of Obstetrics and Gyneacology, Oslo University Hospital, Norway;3. Institute for Experimental Medical Research, Oslo University Hospital, Norway;4. Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Netherlands;5. Department of Obstetrics and Gynecology, University of Groningen, Netherlands;6. University of Oxford, UK;1. Scottish Centre for Production Animal Health and Food Safety, School of Veterinary Medicine, College of Medical Veterinary and Life Sciences, University of Glasgow, Bearsden Road, Glasgow G61 1QH, United Kingdom;2. University of Edinburgh, Royal (Dick) School of Veterinary Studies, Easter Bush Veterinary Centre, Roslin, Midlothian, Scotland EH25 9RG, United Kingdom;1. Department of Otolaryngology-Head and Neck Surgery, Center for Otolaryngology-Head & Neck Surgery of Chinese PLA, Changhai Hospital, Second Military Medical University, Shanghai, China;2. Hearing and Balance Research Unit, Field of Otolaryngology, School of Medicine, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland |
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| Abstract: | Toll-like receptor 4 (TLR-4) mediates Gram-negative bacterial-induced inflammatory responses, including production of pro-inflammatory cytokines. Maternal infection and inflammation play an important role in preterm birth and neonatal brain damage. The localization of placental TLR-4 as well as changes during normal gestation are critical issues in understanding the role of toll-like receptors in defending the placento-fetal unit from maternal infection. We therefore investigated, by immunohistochemistry (IHC) and Western blot, the subcellular localization of TLR-4 in first trimester and term human placenta. In both term placenta (n=4) and first trimester placenta villous samples (n=5), immunoreactivity for TLR-4 was found in the cytoplasm of the syncytiotrophoblast, with darker staining in some areas of the maternal facing plasma membrane (MVM). In addition, TLR-4 was found to be expressed in the first trimester cytotrophoblast cells. Using Western blot analysis, TLR-4 was identified in both placental homogenates and isolated MVM and the fetal facing basal membrane (BM). TLR-4 expression in MVM was significantly higher in term (n=9) as compared to first trimester (n=2) samples. We have shown for the first time that the subcellular localization of TLR-4 in term placenta is preferentially in the MVM compared to BM. The MVM is continuously bathed in maternal blood, suggesting that from this vantage point TLR-4 can initiate a rapid response to maternal bacterial infection. |
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