American Journal of Obstetrics & Gynecology
Volume 201, Issue 3 , Pages 284.e1-284.e7 , September 2009

The negative regulators of the host immune response: an unexplored pathway in preterm birth

Presented at the 29th Annual Meeting of the Society for Maternal-Fetal Medicine, San Diego, CA, Jan. 26-31, 2009.

Received 27 February 2009 ,Revised 21 April 2009 ,Accepted 27 May 2009.

References 

  1. Elovitz MA. Anti-inflammatory interventions in pregnancy: now and the future. Semin Fetal Neonatal Med. 2006;11:327–332
  2. Elovitz MA, Mrinalini C. Animal models of preterm birth. Trends Endocrinol Metab. 2004;15:479–487
  3. Goldenberg RL, Hauth JC, Andrews WW. Intrauterine infection and preterm delivery. N Engl J Med. 2000;342:1500–1507
  4. Goncalves LF, Chaiworapongsa T, Romero R. Intrauterine infection and prematurity. Ment Retard Dev Disabil Res Rev. 2002;8:3–13
  5. Dammann O, Leviton A. Maternal intrauterine infection, cytokines, and brain damage in the preterm newborn. Pediatr Res. 1997;42:1–8
  6. Hirsch E, Blanchard R, Mehta SP. Differential fetal and maternal contributions to the cytokine milieu in a murine model of infection-induced preterm birth. Am J Obstet Gynecol. 1999;180:429–434
  7. Yoon BH, Romero R, Yang SH, et al. Interleukin-6 concentrations in umbilical cord plasma are elevated in neonates with white matter lesions associated with periventricular leukomalacia. Am J Obstet Gynecol. 1996;174:1433–1440
  8. Wang X, Hagberg H, Mallard C, et al. Disruption of interleukin-18, but not interleukin-1, increases vulnerability to preterm delivery and fetal mortality after intrauterine inflammation. Am J Pathol. 2006;169:967–976
  9. Yoshimura K, Hirsch E. Interleukin-6 is neither necessary nor sufficient for preterm labor in a murine infection model. J Soc Gynecol Investig. 2003;10:423–427
  10. Yoshimura K, Hirsch E. Effect of stimulation and antagonism of interleukin-1 signaling on preterm delivery in mice. J Soc Gynecol Investig. 2005;12:533–538
  11. Gonzalez JM, Xu H, Ofori E, Elovitz MA. Toll-like receptors in the uterus, cervix, and placenta: is pregnancy an immunosuppressed state?. Am J Obstet Gynecol. 2007;197:296e1-6
  12. Abrahams VM, Bole-Aldo P, Kim YM, et al. Divergent trophoblast responses to bacterial products mediated by TLRs. J Immunol. 2004;173:4286–4296
  13. 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;163:2103–2111
  14. 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
  15. Gottipati S, Rao NL, Fung-Leung WP. IRAK1: a critical signaling mediator of innate immunity. Cell Signal. 2008;20:269–276
  16. Gan L, Li L. Regulations and roles of the interleukin-1 receptor associated kinases (IRAKs) in innate and adaptive immunity. Immunol Res. 2006;35:295–302
  17. Dillon S, Agrawal A, Van Dyke T, et al. A Toll-like receptor 2 ligand stimulates Th2 responses in vivo, via induction of extracellular signal-regulated kinase mitogen-activated protein kinase and c-Fos in dendritic cells. J Immunol. 2004;172:4733–4743
  18. Echchannaoui H, Frei K, Schnell C, Leib SL, Zimmerli W, Landmann R. Toll-like receptor 2-deficient mice are highly susceptible to Streptococcus pneumoniae meningitis because of reduced bacterial clearing and enhanced inflammation. J Infect Dis. 2002;186:798–806
  19. Fukata M, Michelsen KS, Eri R, et al. Toll-like receptor-4 is required for intestinal response to epithelial injury and limiting bacterial translocation in a murine model of acute colitis. Am J Physiol Gastrointest Liver Physiol. 2005;288:G1055–G1065
  20. Chen G, Shi J, Jin W, et al. Progesterone administration modulates TLRs/NF-kappaB signaling pathway in rat brain after cortical contusion. Ann Clin Lab Sci. 2008;38:65–74
  21. Kobayashi K, Hernandez LD, Galan JE, Janeway CA, Medzhitov R, Flavell RA. IRAK-M is a negative regulator of Toll-like receptor signaling. Cell. 2002;110:191–202
  22. Zhande R, Dauphinee SM, Thomas JA, Yamamoto M, Akira S, Karsan A. FADD negatively regulates lipopolysaccharide signaling by impairing interleukin-1 receptor-associated kinase 1-MyD88 interaction. Mol Cell Biol. 2007;27:7394–7404
  23. Lang T, Mansell A. The negative regulation of Toll-like receptor and associated pathways. Immunol Cell Biol. 2007;85:425–434
  24. Borysiewicz E, Fil D, Konat GW. Rho proteins are negative regulators of TLR2, TLR3, and TLR4 signaling in astrocytes. J Neurosci Res. 2009;87:1565–1572
  25. Baetz A, Frey M, Heeg K, Dalpke AH. Suppressor of cytokine signaling (SOCS) proteins indirectly regulate toll-like receptor signaling in innate immune cells. J Biol Chem. 2004;279:54708–54715
  26. Albrecht V, Hofer TP, Foxwell B, Frankenberger M, Ziegler-Heitbrock L. Tolerance induced via TLR2 and TLR4 in human dendritic cells: role of IRAK-1. BMC Immunol. 2008;9:69
  27. Balaci L, Spada MC, Olla N, et al. IRAK-M is involved in the pathogenesis of early-onset persistent asthma. Am J Hum Genet. 2007;80:1103–1114
  28. Follett PL, Deng W, Dai W, et al. Glutamate receptor-mediated oligodendrocyte toxicity in periventricular leukomalacia: a protective role for topiramate. J Neurosci. 2004;24:4412–4420
  29. Balachandran S, Thomas E, Barber GN. A FADD-dependent innate immune mechanism in mammalian cells. Nature. 2004;432:401–405
  30. Elovitz M, Wang Z. Medroxyprogesterone acetate, but not progesterone, protects against inflammation-induced parturition and intrauterine fetal demise. Am J Obstet Gynecol. 2004;190:693–701
  31. Elovitz MA, Mrinalini C. Can medroxyprogesterone acetate alter Toll-like receptor expression in a mouse model of intrauterine inflammation?. Am J Obstet Gynecol. 2005;193:1149–1155
  32. Elovitz MA, Mrinalini C. The use of progestational agents for preterm birth: lessons from a mouse model. Am J Obstet Gynecol. 2006;195:1004–1010
  33. Elovitz MA, Gonzalez J. Medroxyprogesterone acetate modulates the immune response in the uterus, cervix and placenta in a mouse model of preterm birth. J Matern Fetal Neonatal Med. 2008;21:223–230
  34. Elovitz MA, Mrinalini C, Sammel MD. Elucidating the early signal transduction pathways leading to fetal brain injury in preterm birth. Pediatr Res. 2006;59:50–55
  35. Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH. Progesterone and the risk of preterm birth among women with a short cervix. N Engl J Med. 2007;357:462–469
  36. Meis PJ, Klebanoff M, Thom E, et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003;348:2379–2385
  37. Xu H, Gonzalez JM, Ofori E, Elovitz MA. Preventing cervical ripening: the primary mechanism by which progestational agents prevent preterm birth?. Am J Obstet Gynecol. 2008;198:314e1-8
  38. Yellon SM, Mackler AM, Kirby MA. The role of leukocyte traffic and activation in parturition. J Soc Gynecol Investig. 2003;10:323–338
  39. Matsuguchi T, Musikacharoen T, Ogawa T, Yoshikai Y. Gene expressions of Toll-like receptor 2, but not Toll-like receptor 4, is induced by LPS and inflammatory cytokines in mouse macrophages. J Immunol. 2000;165:5767–5772
  40. Matsumura T, Ito A, Takii T, Hayashi H, Onozaki K. Endotoxin and cytokine regulation of toll-like receptor (TLR) 2 and TLR4 gene expression in murine liver and hepatocytes. J Interferon Cytokine Res. 2000;20:915–921
  41. Zarember KA, Godowski PJ. Tissue expression of human Toll-like receptors and differential regulation of Toll-like receptor mRNAs in leukocytes in response to microbes, their products, and cytokines. J Immunol. 2002;168:554–561
  42. da Fonseca EB, Bittar RE, Carvalho MH, Zugaib M. Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study. Am J Obstet Gynecol. 2003;188:419–424
  43. O'Brien JM, Adair CD, Lewis DF, et al. Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2007;30:687–696
  44. Dudley DJ, Branch DW, Edwin SS, Mitchell MD. Induction of preterm birth in mice by RU486. Biol Reprod. 1996;55:992–995
  45. Reznikov LL, Fantuzzi G, Selzman CH, et al. Utilization of endoscopic inoculation in a mouse model of intrauterine infection-induced preterm birth: role of interleukin 1beta. Biol Reprod. 1999;60:1231–1238
  46. Arcaroli J, Silva E, Maloney JP, et al. Variant IRAK-1 haplotype is associated with increased nuclear factor-kappaB activation and worse outcomes in sepsis. Am J Respir Crit Care Med. 2006;173:1335–1341

 This study was supported in part by March of Dimes Grants 6-FY06-312 and R01HD046544-05.

 Reprints not available from the authors.

 Cite this article as: Lyttle B, Chai J, Gonzalez JM, et al. The negative regulators of the host immune response: an unexplored pathway in preterm birth. Am J Obstet Gynecol 2009;201:284.e1-7.

PII: S0002-9378(09)00564-X

doi: 10.1016/j.ajog.2009.05.053

American Journal of Obstetrics & Gynecology
Volume 201, Issue 3 , Pages 284.e1-284.e7 , September 2009