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BMC Pregnancy and Childbirth
Published in: BMC Pregnancy and Childbirth 1/2010

Open Access 01-12-2010 | Research article

Spontaneous preterm labor is associated with an increase in the proinflammatory signal transducer TLR4 receptor on maternal blood monocytes

Authors: Edyta Pawelczyk, Bogdan J Nowicki, Michael G Izban, Siddharth Pratap, Nupur A Sashti, Maureen Sanderson, Stella Nowicki

Published in: BMC Pregnancy and Childbirth | Issue 1/2010

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Abstract

Background

Localized inflammation and increased expression of TLR4 receptors within the uterus has been implicated in the pathogenesis of preterm labor. It remains unclear whether intrauterine inflammatory responses activate the maternal peripheral circulatory system. Therefore we determined whether increased TLR4 expression is present in the peripheral maternal white blood cells of women with spontaneous preterm labor.

Methods

This is a cross-sectional study of 41 preterm labor cases and 41 non-preterm controls. For each case and control sample, RNA was purified from white blood cells and TLR4 mRNA pool size was evaluated by quantitative PCR. Protein expression levels were determined by flow cytometry. Statistical evaluation using multiple linear regressions was used to determine any significant differences between the cases and controls. The purpose was to determine association prevalence of TLR4 levels and preterm labor.

Results

Adjusted mean TLR4 mRNA levels of 0.788 ± 0.037 (standard error) for preterm labor and 0.348 ± 0.038 for the corresponding pregnant control women were statistically significantly different (P = 0.002). Using the lower 95% confidence interval of the mean expression level in PTL subjects (0.7) as a cutoff value for elevated TLR4 mRNA levels, 25/41 (60.9%) of PTL patients expressed elevated TLR4 mRNA as compared to 0/41 (0%) in control subjects. The TLR4 receptor levels in the granulocyte fraction of white blood cells from preterm labor and pregnant controls were similar. However, TLR4+/CD14+monocytes were 2.3 times more frequent (70% vs. 30%) and TLR4 also had a 2.6-fold higher density (750 vs. 280 molecules per cell) in preterm labor women compared with pregnant controls. There was no difference in the levels of TLR4 in patients at term.

Conclusions

Patients with preterm labor exhibited elevated levels of CD14+ maternal blood monocytes each bearing enhanced expression of TLR4, indicating that the peripheral circulatory system is activated in patients with preterm labor. Elevated leukocyte TLR4 levels may be a useful biomarker associated with preterm labor.
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Literature
1.
Goldenberg RL, Culhane JF, Iams JD, Romero R: Epidemiology and causes of preterm birth. The Lancet. 2008, 371: 75-84. 10.1016/S0140-6736(08)60074-4.CrossRef
2.
Moore ML: Preterm Labor and Birth: What Have We Learned in the Past Two Decades?. Journal of Obstetric, Gynecologic, & Neonatal Nursing. 2003, 32: 638-649.CrossRef
3.
Nicholson WK, Frick KD, Powe NR: Economic Burden of Hospitalizations for Preterm Labor in the United States. Obstet Gynecol. 2000, 96: 95-101. 10.1016/S0029-7844(00)00863-2.PubMed
4.
Haas JS, Fuentes-Afflick E, Stewart AL, Jackson RA, Dean ML, Brawarsky P, Escobar GJ: Prepregnancy Health Status and the Risk of Preterm Delivery. Arch Pediatr Adolesc Med. 2005, 159: 58-63. 10.1001/archpedi.159.1.58.CrossRefPubMed
5.
Robinson JN, Regan JA, Norwitz ER: The epidemiology of preterm labor. Seminars in Perinatology. 2001, 25: 204-214. 10.1053/sper.2001.27548.CrossRefPubMed
6.
Mueller-Heubach E, RUubbistein DN, Schwarz SS: Histologic Chorioamnionitis and Preterm Delivery in Different Patient Populations. Obstet Gynecol. 1990, 75: 622-626.PubMed
7.
Goldenberg RL, Hauth JC, Andrews WW: Intrauterine Infection and Preterm Delivery. N Engl J Med. 2000, 342: 1500-1507. 10.1056/NEJM200005183422007.CrossRefPubMed
8.
DiGiulio DB, Romero R, Amogan HP, Kusanovic JP, Bik EM, Gotsch F, Kim CJ, Erez O, Edwin S, Relman DA: Microbial prevalence, diversity and abundance in amniotic fluid during preterm labor: a molecular and culture-based investigation. PLoS ONE. 2008, 3: e3056-10.1371/journal.pone.0003056.CrossRefPubMedPubMedCentral
9.
Arntzen KJ, Kjollesdal AM, Halgunset J, Vatten L, Austgulen R: TNF, IL-1, IL-6, IL-8 and soluble TNF receptors in relation to chorioamnionitis and premature labor. J Perinat Med. 1998, 26: 17-26. 10.1515/jpme.1998.26.1.17.CrossRefPubMed
10.
Dudley DJ: Pre-term labor: an intra-uterine inflammatory response syndrome?. Journal of Reproductive Immunology. 1997, 36: 93-109. 10.1016/S0165-0378(97)00065-X.CrossRefPubMed
11.
Romero R, Mazor M, Sepulveda W, Avila C, Copeland D, Williams J: Tumor necrosis factor in preterm and term labor. Am J Obstet Gynecol. 1992, 166: 1576-1587.CrossRefPubMed
12.
Wang H, Hirsch E: Bacterially-Induced Preterm Labor and Regulation of Prostaglandin-Metabolizing Enzyme Expression in Mice: The Role of Toll-Like Receptor 4. Biol Reprod. 2003, 69: 1957-1963. 10.1095/biolreprod.103.019620.CrossRefPubMed
13.
Sabroe I, Jones EC, Usher LR, Whyte MKB, Dower SK: Toll-Like Receptor (TLR)2 and TLR4 in Human Peripheral Blood Granulocytes: A Critical Role for Monocytes in Leukocyte Lipopolysaccharide Responses. J Immunol. 2002, 168: 4701-4710.CrossRefPubMed
14.
Janeway CA, Medzhitov R: Innate Immune Recognition. Annual Review of Immunology. 2002, 20: 197-216. 10.1146/annurev.immunol.20.083001.084359.CrossRefPubMed
15.
Medzhitov R, Janeway CA: Decoding the Patterns of Self and Nonself by the Innate Immune System. Science. 2002, 296: 298-300. 10.1126/science.1068883.CrossRefPubMed
16.
Kopp E, Medzhitov R: Recognition of microbial infection by Toll-like receptors. Current Opinion in Immunology. 2003, 15: 396-401. 10.1016/S0952-7915(03)00080-3.CrossRefPubMed
17.
Medzhitov R, Preston-Hurlburt P, Janeway CA: A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature. 1997, 388: 394-397. 10.1038/41131.CrossRefPubMed
18.
Poltorak A, He X, Smirnova I, Liu MY, Huffel CV, Du X, Birdwell D, Alejos E, Silva M, Galanos C, et al: Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in Tlr4 Gene. Science. 1998, 282: 2085-2088. 10.1126/science.282.5396.2085.CrossRefPubMed
19.
Ohashi K, Burkart V, Flohe S, Kolb H: Cutting Edge: Heat Shock Protein 60 Is a Putative Endogenous Ligand of the Toll-Like Receptor-4 Complex. J Immunol. 2000, 164: 558-561.CrossRefPubMed
20.
Okamura Y, Watari M, Jerud ES, Young DW, Ishizaka ST, Rose J, Chow JC, Strauss JF: The Extra Domain A of Fibronectin Activates Toll-like Receptor 4. J Biol Chem. 2001, 276: 10229-10233. 10.1074/jbc.M100099200.CrossRefPubMed
21.
Dybdahl B, Wahba A, Lien E, Flo TH, Waage A, Qureshi N, Sellevold OFM, Espevik T, Sundan A: Inflammatory Response After Open Heart Surgery: Release of Heat-Shock Protein 70 and Signaling Through Toll-Like Receptor-4. Circulation. 2002, 105: 685-690. 10.1161/hc0602.103617.CrossRefPubMed
22.
Kumazaki K, Nakayama M, Yanagihara I, Suehara N, Wada Y: Immunohistochemical distribution of Toll-like receptor 4 in term and preterm human placentas from normal and complicated pregnancy including chorioamnionitis. Human Pathology. 2004, 35: 47-54. 10.1016/j.humpath.2003.08.027.CrossRefPubMed
23.
Holmlund U, Cebers G, Dahlfors AR, Sandstedt B, Bremme K, Ekstrom ES, Scheynius A: Expression and regulation of the pattern recognition receptors Toll-like receptor-2 and Toll-like receptor-4 in the human placenta. Immunology. 2002, 107: 145-151. 10.1046/j.1365-2567.2002.01491.x.CrossRefPubMedPubMedCentral
24.
Faul F, Erdfelder E, Lang AG, Buchner A: G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007, 39: 175-191.CrossRefPubMed
25.
Norman J, Bollapragada S, Yuan M, Nelson S: Inflammatory pathways in the mechanism of parturition. BMC Pregnancy and Childbirth. 2007, 7: S7-10.1186/1471-2393-7-S1-S7.CrossRefPubMedPubMedCentral
26.
Sabroe I, Prince LR, Jones EC, Horsburgh MJ, Foster SJ, Vogel SN, Dower SK, Whyte MKB: Selective Roles for Toll-Like Receptor (TLR)2 and TLR4 in the Regulation of Neutrophil Activation and Life Span. J Immunol. 2003, 170: 5268-5275.CrossRefPubMed
27.
Haddad R, Tromp G, Kuivaniemi H, Chaiworapongsa T, Kim YM, Mazor M, Romero R: Human spontaneous labor without histologic chorioamnionitis is characterized by an acute inflammation gene expression signature. American Journal of Obstetrics and Gynecology. 2006, 195: 394-10.1016/j.ajog.2005.08.057.CrossRefPubMedPubMedCentral
28.
Makidono C, Mizuno M, Nasu J, Hiraoka S, Okada H, Yamamoto K, Fujita T, Shiratori Y: Increased serum concentrations and surface expression on peripheral white blood cells of decay-accelerating factor (cd55) in patients with active ulcerative colitis. Journal of Laboratory and Clinical Medicine. 2004, 143: 152-158. 10.1016/j.lab.2003.11.004.CrossRefPubMed
29.
Nowicki S, Izban MG, Pawelczyk E, Agboto VK, Pratap S, Olson G, Nowicki B: Preterm labor: CD55 in maternal blood leukocytes. Am J Reprod Immunol. 2009, 61 (5): 360-7. 10.1111/j.1600-0897.2009.00702.x. 2009, 61: 360-367CrossRefPubMed
30.
Yuan M, Jordan F, McInnes I, Harnett MM, Norman JE: Leukocytes are primed in peripheral blood for activation during term and preterm labour. Molecular Human Reproduction. 2009, 15: 713-724. 10.1093/molehr/gap054.CrossRefPubMedPubMedCentral
Metadata
Title
Spontaneous preterm labor is associated with an increase in the proinflammatory signal transducer TLR4 receptor on maternal blood monocytes
Authors
Edyta Pawelczyk
Bogdan J Nowicki
Michael G Izban
Siddharth Pratap
Nupur A Sashti
Maureen Sanderson
Stella Nowicki
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Pregnancy and Childbirth / Issue 1/2010
Electronic ISSN: 1471-2393
DOI
https://doi.org/10.1186/1471-2393-10-66

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