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Modulation of Monocyte Chemotactic Protein-1 Expression During Lipopolysaccharide-Induced Preterm Delivery in the Pregnant Mouse

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Abstract

Preterm delivery is often associated with increased cytokine and chemokine production. These studies characterize the expression of the chemokine monocyte chemotactic protein-1 (MCP-1) in mice during lipopolysaccharide (LPS)—induced preterm delivery. Uterine and other tissues were harvested from CD-1 mice on gestational day 15 after intrauterine LPS injection. Quantitative real-time reverse-transcriptase polymerase chain reactions determined MCP-1 and toll-like receptor 4 (TLR4) mRNA expression during the 24 hours after LPS. MCP-1 protein expression was determined using a cytokine/chemokine protein array, enzyme-linked immunosorbant assay, and immunohistochemistry. Intrauterine LPS injection caused preterm delivery in CD-1 mice between 12 and 24 hours. Expression of MCP-1 mRNA significantly increased at 2 and 6 hours, while TLR4 expression did not significantly change over 24 hours. The MCP-1 protein levels peaked by 2 to 6 hours in maternal serum, liver, lung, kidney, and uterus. Immunohistochemistry confirmed MCP-1 in the myometrium and endometrium. These studies provide evidence suggesting that MCP-1 potentially plays an important role during the proinflammatory immune response, leading to preterm labor in the mouse.

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References

  1. Petrou S. The economic consequences of preterm birth during the first 10 years of life. BJOG. 2005;112(suppl 1):10–15.

    Article  Google Scholar 

  2. Callaghan WM, MacDorman MF, Rasmussen SA, Qin C., Lackritz EM The contribution of preterm birth to infant mortality rates in the United States. Pediatrics. 2006;118(4): 1566–1573.

    Article  Google Scholar 

  3. Hirsch E., Wang H. The molecular pathophysiology of bacterially induced preterm labor: insights from the murine model. J Soc Gynecol Investig. 2005;12(3):145–155.

    Article  CAS  Google Scholar 

  4. Hirsch E., Muhle RA, Mussalli GM, Blanchard R. Bacterially induced preterm labor in the mouse does not require maternal interleukin-1 signaling. Am J Obstet Gynecol. 2002;186(3): 523–530.

    Article  Google Scholar 

  5. Elovitz MA, Wang Z., Chien EK, Rychlik DF, Phillippe M. A new model for inflammation-induced preterm birth: the role of platelet-activating factor and toll-like receptor-4. Am J Pathol. 2003;163(5):2103–2111.

    Article  CAS  Google Scholar 

  6. Törnblom SA, Klimaviciute A., Byström B., Chromek M., Brauner A., Ekman-Ordeberg G. Non-infected preterm parturition is related to increased concentrations of IL-6, IL-8 and MCP-1 in human cervix. Reprod Biol Endocrinol. 2005;3:39.

    Google Scholar 

  7. Yellon SM, Mackler AM, Kirby MA The role of leukocyte traffic and activation in parturition. J Soc Gynecol Investig. 2003;10(6):323–338.

    Article  CAS  Google Scholar 

  8. Lappas M., Permezel M., Georgiou HM, Rice GE Regulation of proinflammatory cytokines in human gestational tissues by peroxisome proliferator-activated receptor-gamma: effect of 15-deoxy-Delta(12,14)-PGJ(2) and troglitazone. J Clin Endocrinol Metab. 2002;87(10):4667–4672.

    Article  CAS  Google Scholar 

  9. Gravett MG, Hitti J., Hess DL, Eschenbach DA Intrauterine infection and preterm delivery: evidence for activation of the fetal hypothalamic-pituitary-adrenal axis. Am J Obstet Gynecol. 2000;182(6):1404–1413.

    Article  CAS  Google Scholar 

  10. Gravett MG, Witkin SS, Haluska GJ, Edwards JL, Cook MJ, Novy MJ An experimental model for intraamniotic infection and preterm labor in rhesus monkeys. Am J Obstet Gynecol. 1994;171(6):1660–1667.

    Article  CAS  Google Scholar 

  11. Leslie KK, Lee SL, Woodcock SM, et al. Acute intrauterine infection results in an imbalance between pro- and antiinflammatory cytokines in the pregnant rabbit. Am J Reprod Immunol. 2000;43(5):305–311.

    Article  CAS  Google Scholar 

  12. Mussalli GM, Brunnert SR, Hirsch E. Preterm delivery in mice with renal abscess. Obstet Gynecol. 2000;95(3):453–456.

    CAS  PubMed  Google Scholar 

  13. Mitsuhashi Y., Otsuki K., Yoda A., Shimizu Y., Saito H., Yanaihara T. Effect of lactoferrin on lipopolysaccharide (LPS) induced preterm delivery in mice. Acta Obstet Gynecol Scand. 2000; 79(5):355–358.

    Article  CAS  Google Scholar 

  14. Reznikov LL, Shames BD, Barton HA, et al. Interleukin-1beta deficiency results in reduced NF-kappaB levels in pregnant mice. Am J Physiol Regul Integr Comp Physiol. 2000; 278(1):R263–R270.

    Article  CAS  Google Scholar 

  15. Romero R., Erez O., Espinoza J. Intrauterine infection, preterm labor, and cytokines. J Soc Gynecol Investig. 2005; 12(7):463–465.

    Article  Google Scholar 

  16. Yoshimura K., Hirsch E. Interleukin-6 is neither necessary nor sufficient for preterm labor in a murine infection model. J Soc Gynecol Investig. 2003;10(7):423–427.

    Article  CAS  Google Scholar 

  17. Jacobsson B., Holst RM, Wennerholm UB, Andersson B., Lilja H., Hagberg H. Monocyte chemotactic protein-1 in cervical and amniotic fluid: relationship to microbial invasion of the amniotic cavity, intra-amniotic inflammation, and preterm delivery. Am J Obstet Gynecol. 2003;189(4):1161–1167.

    Article  CAS  Google Scholar 

  18. Esplin MS, Romero R., Chaiworapongsa T., et al. Monocyte chemotactic protein-1 is increased in the amniotic fluid of women who deliver preterm in the presence or absence of intra-amniotic infection. J Matern Fetal Neonatal Med. 2005; 17(6):365–373.

    Article  CAS  Google Scholar 

  19. Esplin MS, Peltier MR, Hamblin S., et al. Monocyte chemotactic protein-1 expression is increased in human gestational tissues during term and preterm labor. Placenta. 2005:26(8–9): 661–671.

    Article  CAS  Google Scholar 

  20. Boyd JH, Divangahi M., Yahiaoui L., Gvozdic D., Qureshi S., Petrof BJ Toll-like receptors differentially regulate CC and CXC chemokines in skeletal muscle via NF-kappaB and calcineurin. Infect Immun. 2006;74(12):6829–6838.

    Article  CAS  Google Scholar 

  21. Adams KM, Lucas J., Kapur RP, Stevens AM LPS induces translocation of TLR4 in amniotic epithelium. Placenta. 2007; 28(5–6):477–481.

    Article  CAS  Google Scholar 

  22. Baggiolini M., Dahinden CA CC chemokines in allergic inflammation. Immunol Today. 1994;15(3):127–133.

    Article  CAS  Google Scholar 

  23. Lu B., Rutledge BJ, Gu L., et al. Abnormalities in monocyte recruitment and cytokine expression in monocyte chemoattractant protein 1-deficient mice. J Exp Med. 1998;187(4):601–608.

    Article  CAS  Google Scholar 

  24. Rankine EL, Hughes PM, Botham MS, Perry VH, Felton LM Brain cytokine synthesis induced by an intraparenchymal injection of LPS is reduced in MCP-1-deficient mice prior to leucocyte recruitment. Eur J Neurosci. 2006;24(1):77–86.

    Article  CAS  Google Scholar 

  25. Bone-Larson CL, Hogaboam CM, Steinhauser ML, et al. Novel protective effects of stem cell factor in a murine model of acute septic peritonitis: dependence on MCP-1. Am J Pathol. 2000;157(4):1177–1186.

    Article  CAS  Google Scholar 

  26. Warren GL, Hulderman T., Mishra D., et al. Chemokine receptor CCR2 involvement in skeletal muscle regeneration. FASEB J. 2005;19(3):413–415.

    Article  CAS  Google Scholar 

  27. Lund S., Christensen K., Hedtjän A., et al.The dynamics of the LPS triggered inflammatory response of murine microglia under different culture and in vivo conditions. J Neuroimmunol. 2006;180(1–2):71–87.

    Article  CAS  Google Scholar 

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Correspondence to Mark Phillippe MD, MHCM.

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Supported by the National Institute of Child Health and Human Development (grant HD 44747).

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Diamond, A.K., Sweet, L.M., Oppenheimer, K.H. et al. Modulation of Monocyte Chemotactic Protein-1 Expression During Lipopolysaccharide-Induced Preterm Delivery in the Pregnant Mouse. Reprod. Sci. 14, 548–559 (2007). https://doi.org/10.1177/1933719107307792

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  • DOI: https://doi.org/10.1177/1933719107307792

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