Progesterone decreases gut permeability through upregulating occludin expression in primary human gut tissues and Caco-2 cells
Open accessAbstract
Progesterone plays a protective role in preventing inflammation and preterm delivery during pregnancy. However, the mechanism involved is unknown. Microbial product translocation from a permeable mucosa is demonstrated as a driver of inflammation. To study the mechanism of the protective role of progesterone during pregnancy, we investigated the effect of physiologic concentrations of progesterone on tight junction protein occludin expression and human gut permeability in vitro and systemic microbial translocation in pregnant women in vivo. Plasma bacterial lipopolysaccharide (LPS), a representative marker of in vivo systemic microbial translocation was measured. We found that plasma LPS levels were significantly decreased during 24 to 28 weeks of gestation compared to 8 to 12 weeks of gestation. Moreover, plasma LPS levels were negatively correlated with plasma progesterone levels but positively correlated with plasma tumor necrosis factor-alpha (TNF-α) levels at 8 to 12 weeks of gestation but not at 24 to 28 weeks of gestation. Progesterone treatment increased intestinal trans-epithelial electrical resistance (TEER) in primary human colon tissues and Caco-2 cells in vitro through upregulating tight junction protein occludin expression. Furthermore, progesterone exhibited an inhibitory effect on nuclear factor kappa B (NF-κB) activation following LPS stimulation in Caco-2 cells. These results reveal a novel mechanism that progesterone may play an important role in decreasing mucosal permeability, systemic microbial translocation, and inflammation during pregnancy.
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Progesterone upregulated OCLN expression in the gut and inhibited NF-κB activation to maintain gut barrier homeostasis.
“Zhou et al201 reported that progesterone upregulated OCLN expression in the gut and inhibited NF-κB activation to maintain gut barrier homeostasis.”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [201]
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Cites
Epidemiology and causes of preterm birth
Goldenberg, R. L., Culhane, J. F., Iams, J. D., & Romero, R. (2008) · The Lancet · doi:10.1016/s0140-6736(08)60074-4 · Cited by 7,801 · see citing works
Intestinal barrier function: molecular regulation and disease pathogenesis
Groschwitz, K. R., & Hogan, S. P. (2009) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2009.05.038 · Cited by 1,775 · see citing works
Tight junctions: from simple barriers to multifunctional molecular gates
Zihni, C., Mills, C., Matter, K., & Balda, M. S. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.80 · Cited by 1,484 · see citing works
The unique immunological and microbial aspects of pregnancy
Mor, G., Aldo, P., & Alvero, A. B. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.64 · Cited by 1,041 · see citing works
Synthesis of T helper 2-type cytokines at the maternal-fetal interface.
Lin, H., Mosmann, T. R., Guilbert, L. J., Tuntipopipat, S., & Wegmann, T. G. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.9.4562 · Cited by 898 · see citing works
Gadaleta, R. M., van Erpecum, K. J., Oldenburg, B., Willemsen, E. C. L., Renooij, W., Murzilli, S., Klomp, L. W. J., Siersema, P. D., Schipper, M. E. I., Danese, S., et al. (2011) · Gut · doi:10.1136/gut.2010.212159 · Cited by 870 · see citing works
Obesity, inflammation, and the gut microbiota
Cox, A. J., West, N. P., & Cripps, A. W. (2015) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(14)70134-2 · Cited by 869 · see citing works
Hollis, B. W., Johnson, D., Hulsey, T. C., Ebeling, M. D., & Wagner, C. L. (2011) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.463 · Cited by 847 · see citing works
Piccinni, M., Giudizi, M. G., Biagiotti, R., Beloni, L., Giannarini, L., Sampognaro, S., Parronchi, P., Manetti, R., Annunziato, F., & Livi, C. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.155.1.128 · Cited by 743 · see citing works
Pregnancy and pregnancy-associated hormones alter immune responses and disease pathogenesis
Robinson, D. P., & Klein, S. L. (2012) · Hormones and Behavior · doi:10.1016/j.yhbeh.2012.02.023 · Cited by 711 · see citing works
Jiang, W., Lederman, M. M., Hunt, P. W., Sieg, S. F., Haley, K. P., Rodriguez, B. A., LANDAY, A. L., Martin, J. N., Sinclair, E., Asher, A. I., et al. (2009) · The Journal of Infectious Diseases · doi:10.1086/597476 · Cited by 591 · see citing works
Self-citationRegulation of tight junctions and loss of barrier function in pathophysiology
Harhaj, N. S., & Antonetti, D. A. (2003) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2003.08.007 · Cited by 543 · see citing works
Microbial Translocation Across the GI Tract
Brenchley, J. M., & Douek, D. C. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075001 · Cited by 496 · see citing works
Marchiando, A. M., Shen, L., Graham, W. V., Weber, C. R., Schwarz, B. T., Austin, J. R., Raleigh, D. R., Guan, Y., Watson, A. J. M., Montrose, M. H., et al. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.200902153 · Cited by 475 · see citing works
Myosin light chain phosphorylation regulates barrier function by remodeling tight junction structure
Shen, L., Black, E. D., Witkowski, E. D., Lencer, W. I., Guerriero, V., Schneeberger, E. E., & Turner, J. R. (2006) · Journal of Cell Science · doi:10.1242/jcs.02915 · Cited by 467 · see citing works
The role of sex hormones in immune protection of the female reproductive tract
Wira, C. R., Rodríguez‐García, M., & Patel, M. V. (2015) · Nature reviews. Immunology · doi:10.1038/nri3819 · Cited by 448 · see citing works
Raghupathy, R., Makhseed, M., Azizieh, F. Y., Omu, A. E., Gupta, M., & Farhat, R. M. (2000) · Human Reproduction · doi:10.1093/humrep/15.3.713 · Cited by 415 · see citing works
Inflammatory pathways in female reproductive health and disease
Jabbour, H. N., Sales, K. J., Catalano, R. D., & Norman, J. E. (2009) · Reproduction · doi:10.1530/rep-09-0247 · Cited by 368 · see citing works
Vitamin D supplementation in pregnancy: a systematic review
Harvey, N. C., Holroyd, C. R., Ntani, G., Javaid, M. K., Cooper, P., Moon, R. J., Cole, Z. A., Tinati, T., Godfrey, K. M., Dennison, E. M., et al. (2014) · Health Technology Assessment · doi:10.3310/hta18450 · Cited by 352 · see citing works
Regulation of the Anti-Inflammatory Cytokines Interleukin-4 and Interleukin-10 during Pregnancy
Chatterjee, P., Chiasson, V. L., Bounds, K. R., & Mitchell, B. M. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00253 · Cited by 347 · see citing works
Understanding the Complexity of the Immune System during Pregnancy
Racicot, K. E., Kwon, J., Aldo, P. B., Silasi, M., & Mor, G. (2014) · American Journal of Reproductive Immunology · doi:10.1111/aji.12289 · Cited by 337 · see citing works
Actin Depolymerization Disrupts Tight Junctions via Caveolae-mediated Endocytosis
Shen, L., & Turner, J. R. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e04-12-1089 · Cited by 302 · see citing works
The gut microbiota in infants of obese mothers increases inflammation and susceptibility to NAFLD
Soderborg, T. K., Clark, S. E., Mulligan, C. E., Janssen, R. C., Babcock, L. R., Ir, D., Young, B. E., Krebs, N. F., Lemas, D. J., Johnson, L. K., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06929-0 · Cited by 291 · see citing works
Unique aspects of the perinatal immune system
Zhang, X., Zhivaki, D., & Lo-Man, R. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.54 · Cited by 276 · see citing works
Robinson, D. P., Lorenzo, M. E., Jian, W., & Klein, S. L. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002149 · Cited by 257 · see citing works
Cardenas, I., Means, R. E., Aldo, P. B., Koga, K., Lang, S. M., Booth, C. J., Alejandro Manzur, Y., Enrique Oyarzún, E., Romero, R. J., & Mor, G. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1000289 · Cited by 248 · see citing works
The influence of pregnancy on systemic immunity
Pazos, M. A., SPERLING, R. S., Moran, T. M., & Kraus, T. (2012) · Immunologic Research · doi:10.1007/s12026-012-8303-9 · Cited by 247 · see citing works
Progesterone treatment inhibits the inflammatory agents that accompany traumatic brain injury
Pettus, E. H., Wright, D. W., Stein, D. G., & Hoffman, S. W. (2005) · Brain Research · doi:10.1016/j.brainres.2005.05.004 · Cited by 235 · see citing works
Smith, R., Smith, J. I., Shen, X., Engel, P. J., Bowman, M. E., McGrath, S. A., Bisits, A. M., McElduff, P., Giles, W. B., & Smith, D. W. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-2257 · Cited by 194 · see citing works
Cook, J., Hislop, J., Adewuyi, T., Harrild, K., Altman, D., Ramsay, C., Fraser, C., Buckley, B., Fayers, P., Harvey, I., et al. (2014) · Health Technology Assessment · doi:10.3310/hta18280 · Cited by 194 · see citing works
Braniste, V., Leveque, M., Buisson‐Brenac, C., Bueno, L. P., Fioramonti, J., & Houdeau, É. (2009) · The Journal of Physiology · doi:10.1113/jphysiol.2009.169300 · Cited by 161 · see citing works
Marshall, J. S., Leal‐Berumen, I., Nielsen, L., Glibetić, M., & Jordana, M. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118506 · Cited by 156 · see citing works
Anti-Inflammatory Effects of Progesterone in Lipopolysaccharide-Stimulated BV-2 Microglia
Lei, B., Mace, B. E., Dawson, H. N., Warner, D. S., Laskowitz, D. T., & James, M. L. (2014) · PLoS ONE · doi:10.1371/journal.pone.0103969 · Cited by 140 · see citing works
Carrasco‐Pozo, C., Morales, P., & Gotteland, M. (2013) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf400150p · Cited by 138 · see citing works
Steroid hormones and disease activity during pregnancy in systemic lupus erythematosus
Doria, A., Cutolo, M., Ghirardello, A., Zampieri, S., Vescovi, F., Sulli, A., Giusti, M., Piccoli, A., Grella, P., & Gambari, P. F. (2002) · Arthritis Care & Research · doi:10.1002/art.10248 · Cited by 130 · see citing works
Lissauer, D. M., Eldershaw, S. A., Inman, C. F., Coomarasamy, A., Moss, P. A. H., & Kilby, M. D. (2015) · European Journal of Immunology · doi:10.1002/eji.201445404 · Cited by 130 · see citing works
Cutting Edge: Progesterone Regulates IFN-α Production by Plasmacytoid Dendritic Cells
Hughes, G. C., Thomas, S., Li, C., et al. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.4.2029 · Cited by 129 · see citing works
Lee, J., Lydon, J., & Kim, C. H. (2012) · European Journal of Immunology · doi:10.1002/eji.201142317 · Cited by 129 · see citing works
Sayeed, I., Parvez, S., Wali, B., Siemen, D., & Stein, D. G. (2009) · Brain Research · doi:10.1016/j.brainres.2009.01.045 · Cited by 116 · see citing works
Fasano, A. (2008) · American Journal Of Pathology · doi:10.2353/ajpath.2008.080192 · Cited by 110 · see citing works
Hormonal modulation of the immune system — A spotlight on the role of progestogens
Tan, I. J., Peeva, E., & Zandman‐Goddard, G. (2015) · Autoimmunity Reviews · doi:10.1016/j.autrev.2015.02.004 · Cited by 110 · see citing works
Ye, L., Martin, T. A., Parr, C., et al. (2003) · Journal of Cellular Physiology · doi:10.1002/jcp.10315 · Cited by 96 · see citing works
Wagner, C. L., Baggerly, C. A., McDonnell, S. L., et al. (2014) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2014.11.013 · Cited by 86 · see citing works
Vitamin D and Inflammatory Cytokines in Healthy and Preeclamptic Pregnancies
Barrera, D., Dı́az, L., Noyola-Martínez, N., et al. (2015) · Nutrients · doi:10.3390/nu7085293 · Cited by 85 · see citing works
Si, D., Li, J., Liu, J., Wang, X., Wei, Z., Tian, Q.-Y., Wang, H., & Liu, G. (2014) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2014.1840 · Cited by 67 · see citing works
In vivo immune signatures of healthy human pregnancy: Inherently inflammatory or anti-inflammatory?
Graham, C., Chooniedass, R., Stefura, W. P., Becker, A. B., Sears, M. R., Turvey, S. E., Mandhane, P. J., Subbarao, P., CHILD Study Investigators, & HayGlass, K. T. (2017) · PLoS ONE · doi:10.1371/journal.pone.0177813 · Cited by 56 · see citing works
Estrogen decreases tight junction protein ZO-1 expression in human primary gut tissues
Zhou, Z., Zhang, L., Ding, M., Luo, Z., Shao, Y., Bansal, M. B., Gilkeson, G. S., Lang, R., & Jiang, W. (2017) · Clinical Immunology · doi:10.1016/j.clim.2017.08.019 · Cited by 55 · see citing works
Self-citationVitamin D: a steroid hormone with progesterone-like activity.
Monastra, G., Grazia, S. D., Luca, L. D., et al. (2018) · PubMed · doi:10.26355/eurrev_201804_14845 · Cited by 50 · see citing works
López, M., Figueras, F., Coll, O., et al. (2015) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiv416 · Cited by 45 · see citing works
Ovarian Dendritic Cells Act as a Double-Edged Pro-Ovulatory and Anti-Inflammatory Sword
Cohen-Fredarow, A., Tadmor, A., Raz, T., et al. (2014) · Molecular Endocrinology · doi:10.1210/me.2013-1400 · Cited by 44 · see citing works
Female Sex Hormones Modulate the Function of LPS‐treated Macrophages
Chao, T., Chao, H.-H., Chen, M., et al. (2000) · American Journal of Reproductive Immunology · doi:10.1111/j.8755-8920.2000.440511.x · Cited by 41 · see citing works
Effect of estrogen on the expression of occludin in ovariectomized mouse brain
Kang, H. S., Ahn, H. S., Kang, H. J., & Gye, M. C. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.03.052 · Cited by 37 · see citing works
Piosik, Z. M., Goegebeur, Y., Klitkou, L., Steffensen, R., & Christiansen, O. B. (2013) · American Journal of Reproductive Immunology · doi:10.1111/aji.12135 · Cited by 37 · see citing works
Sumanasekera, W. K., Sumanasekera, G., Mattingly, K. A., Dougherty, S. M., Keynton, R. S., & Klinge, C. M. (2007) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00418.2006 · Cited by 33 · see citing works
Yu, P., Li, S., Zhang, Z., Wen, X., Quan, W., Tian, Q., Gao, C., Su, W., Zhang, J., & Jiang, R. (2017) · Cell Proliferation · doi:10.1111/cpr.12362 · Cited by 33 · see citing works
Maternal obesity is associated with a low serum progesterone level in early pregnancy
Goh, J. Y., He, S., Allen, J. C., et al. (2016) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2015-0030 · Cited by 32 · see citing works
Jiang, W., Younes, S., Funderburg, N., Mudd, J. C., Espinosa, E., Davenport, M. P., Babineau, D. C., Sieg, S. F., & Lederman, M. M. (2014) · Journal of Virology · doi:10.1128/jvi.00017-14 · Cited by 30 · see citing works
Self-citationKuruca, S. E., Karadenizli, S., Akgün‐Dar, K., Kapucu, A., Kaptan, Z., & Üzüm, G. (2017) · Acta Histochemica · doi:10.1016/j.acthis.2017.07.005 · Cited by 29 · see citing works
Early pregnancy vitamin D and patterns of antenatal inflammation in African–American women
Bobbitt, K. R., Peters, R. M., Li, J., et al. (2014) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2014.09.054 · Cited by 25 · see citing works
Velayudhan, B. T., Huderson, B. P., Ellis, S. E., et al. (2014) · Domestic Animal Endocrinology · doi:10.1016/j.domaniend.2014.10.002 · Cited by 17 · see citing works
Zhang, L., Luo, Z., Sieg, S. F., Funderburg, N., Yu, X., Fu, P., Wu, H., Jiao, Y., Gao, Y., Greenspan, N. S., et al. (2014) · Journal of Virology · doi:10.1128/jvi.00682-14 · Cited by 15 · see citing works
Self-citationP016 Pregnancy in IBD: direct effect of sex-hormones on epithelial barrier function
van der Giessen, J., van der Woude, C. J., Peppelenbosch, M. P., & Fuhler, G. M. (2017) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjx002.142 · Cited by 3 · see citing works
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Regulation of Intestinal Barrier Function by Microbial Metabolites
Ghosh, S., Whitley, C. S., Haribabu, B., & Jala, V. R. (2021) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2021.02.007 · Cited by 835 · see citing works
- Authors
- Zhou, Z., Bian, C., Luo, Z., Guille, C., Ogunrinde, E., Wu, J., Zhao, M., Fitting, S., Kamen, D. L., Oates, J. C., Gilkeson, G., & Jiang, W.
- Affiliations
- Medical University of South Carolina (US)
- Jiangsu University (CN)
- Whitman College (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Gilkeson, Gary
- Jiang, Wei
- ORCID
- Venue
- Scientific Reports
- Published
- 2019-06-10
- Volume
- 9
- Issue
- 1
- Pages
- 8367-8367
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC6558054
- OpenAlex
- W2948138973
- Cited by
- 78
- References
- 62
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 6 · 2023: 12 · 2022: 12 · 2021: 21 · 2020: 3 · 2019: 3
- FWCI
- 7.42
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (K12HD055885)
- U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (K23DA039318, DA045596)
- U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (P60 AR062755)
- U.S. Department of Veterans Affairs (CX001211)
- DH | NIHR | Efficacy and Mechanism Evaluation Programme (P30AR072582)
- DH | NIHR | Health Services Research Programme (AR068406)
- DH | NIHR | Health Services and Delivery Research Programme (RR001070)
- Topics
- Health Sciences › Medicine › Epidemiology › Preterm Birth and Chorioamnionitis
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Keywords
- progesterone, intestinal permeability, occludin, tight junctions, microbial translocation, lipopolysaccharide, pregnancy, intestinal inflammation, TNF-α, NF-κB, transepithelial electrical resistance, Caco-2 cells, preterm birth
- MeSH terms
- Gastrointestinal Microbiome, Adult, Female, Gene Expression Regulation, Humans, Inflammation, Intestinal Mucosa, Lipopolysaccharides, Permeability, Pregnancy, Progesterone, Tumor Necrosis Factor-alpha, Caco-2 Cells, Tight Junctions, Premature Birth, Occludin
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