DOI QR코드

DOI QR Code

Dexmedetomidine and LPS co-treatment attenuates inflammatory response on WISH cells via inhibition of p38/NF-kB signaling pathway

  • Kim, Tae-Sung (Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Pusan National University, Dental Research Institute) ;
  • Yoon, Ji-Young (Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Pusan National University, Dental Research Institute) ;
  • Kim, Cheul-Hong (Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Pusan National University, Dental Research Institute) ;
  • Choi, Eun-Ji (Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Pusan National University, Dental Research Institute) ;
  • Kim, Yeon Ha (Department of Integrated Biological Science, Pusan National University) ;
  • Kim, Eun-Jung (Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Pusan National University, Dental Research Institute)
  • 투고 : 2022.07.04
  • 심사 : 2022.07.16
  • 발행 : 2022.08.01

초록

Background: Inflammatory dental diseases that occur during pregnancy can cause preterm labor and/or intrauterine growth restriction. Therefore, proactive treatment of dental diseases is necessary during pregnancy. Dexmedetomidine (DEX) is a widely used sedative in the dental field, but research on the effect of DEX on pregnancy is currently insufficient. In this study, we investigated the effects of co-treatment with DEX and lipopolysaccharide (LPS) on inflammatory responses in human amnion-derived WISH cells. Methods: Human amnion-derived WISH cells were treated with 0.001, 0.01, 0.1, and 1 ㎍/mL DEX with 1 ㎍/mL LPS for 24 h. Cytotoxicity of WISH cells was evaluated by 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assay. The protein expression of cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), p38, and nuclear factor kappa B (NF-𝜅B) was examined by western blot analysis. The mRNA expression of pro-inflammatory cytokines such as interleukin (IL)-1𝛽 and tumor necrosis factor (TNF)-𝛼 was analyzed by real-time quantitative polymerase chain reaction. Results: Co-treatment with DEX and LPS showed no cytotoxicity in the WISH cells. The mRNA expression of IL-1𝛽 and TNF-𝛼 decreased after co-treatment with DEX and LPS. DEX and LPS co-treatment decreased the protein expression of COX-2, PGE2, phospho-p38, and phospho-NF-𝛋B in WISH cells. Conclusion: Co-treatment with DEX and LPS suppressed the expression of COX-2 and PGE2, as well as pro-inflammatory cytokines such as IL-1𝛽 and TNF-𝛼 in WISH cells. In addition, the anti-inflammatory effect of DEX and LPS co-treatment was mediated by the inhibition of p38/NF-𝜅B activation.

키워드

과제정보

This work was supported by a 2-Year Research grant from the Pusan National University.

참고문헌

  1. Gajendra S, Kumar JV. Oral health and pregnancy: a review. N Y State Dent J 2004; 70: 40-4.
  2. Jang KA, Kim KO, Lee SO. Comparing oral health care awareness and practice in pregnant women with and without oral health education experience. J Korean Soc Matern Child Health 2016; 20: 169-77. https://doi.org/10.21896/jksmch.2016.20.2.169
  3. Park JH, Lee KS. Comparison of oral care patterns before and during the pregnancy. J Dent Hyg Sci 2011; 11: 273-8.
  4. Saraiva MC, Bettiol H, Barbieri MA, Silva AA. Are intrauterine growth restriction and preterm birth associated with dental caries? Community Dent Oral Epidemiol 2007; 35: 364-76. https://doi.org/10.1111/j.1600-0528.2006.00345.x
  5. Harjunmaa U, Jarnstedt J, Alho L, Dewey KG, Cheung YB, Deitchler M, et al. Association between maternal dental periapical infections and pregnancy outcomes: results from a cross-sectional study in Malawi. Trop Med Int Health 2015; 20: 1549-58. https://doi.org/10.1111/tmi.12579
  6. Romero R, Espinoza J, Kusanovic JP, Gotsch F, Hassan S, Erez O, et al. The preterm parturition syndrome. BJOG 2006; 113: 17-42.
  7. Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet 2008; 371: 75-84. https://doi.org/10.1016/S0140-6736(08)60074-4
  8. DiGiulio DB, Romero R, Kusanovic JP, Gomez R, Kim CJ, Seok KS, et al. Prevalence and diversity of microbes in the amniotic fluid, the fetal inflammatory response, and pregnancy outcome in women with preterm pre-labor rupture of membranes. Am J Reprod Immunol 2010; 64: 38-57. https://doi.org/10.1111/j.1600-0897.2010.00830.x
  9. Gillaux C, Mehats C, Vaiman D, Cabrol D, Breuiller-Fouche M. Functional screening of TLRs in human amniotic epithelial cells. J Immunol 2011; 187: 2766-74. https://doi.org/10.4049/jimmunol.1100217
  10. Abe Y, Komatsubara M, Saito M, Toda M, Shinozaki H, Tamura T, et al. Activin A is stimulated by tumor necrosis factor-alpha and modulates collagen gene expression in human amniotic cells. J Endocrinol Invest 2013; 36: 515-20. https://doi.org/10.3275/8816
  11. Christiaens I, Zaragoza DB, Guilbert L, Robertson SA, Mitchell BF, Olson DM. Inflammatory processes in preterm and term parturition. J Reprod Immunol 2008; 79: 50-7. https://doi.org/10.1016/j.jri.2008.04.002
  12. Nancy P, Erlebacher A. T cell behavior at the maternal-fetal interface. Int J Dev Biol 2014; 58: 189-98. https://doi.org/10.1387/ijdb.140054ae
  13. Premyslova M, Li W, Alfaidy N, Bocking AD, Campbell K, Gibb W, et al. Differential expression and regulation of microsomal prostaglandin E(2) synthase in human fetal membranes and placenta with infection and in cultured trophoblast cells. J Clin Endocrinol Metab 2003; 88: 6040-7. https://doi.org/10.1210/jc.2003-030618
  14. Pavan B, Buzzi M, Ginanni-Corradini F, Ferretti ME, Vesce F, Biondi C. Influence of oxytocin on prostaglandin E2, intracellular calcium, and cyclic adenosine monophosphate in human amnion-derived (WISH) cells. Am J Obstet Gynecol 2000; 183: 76-82. https://doi.org/10.1016/S0002-9378(00)13874-8
  15. Kaur M, Singh PM. Current role of dexmedetomidine in clinical anesthesia and intensive care. Anesth Essays Res 2011; 5: 128-33. https://doi.org/10.4103/0259-1162.94750
  16. Maze M, Scarfini C, Cavaliere F. New agents for sedation in the intensive care unit. Crit Care Clin 2001; 17: 881-97. https://doi.org/10.1016/s0749-0704(05)70185-8
  17. Mattingly JE, D'Alessio J, Ramanathan J. Effects of obstetric analgesics and anesthetics on the neonate : a review. Paediatr Drugs 2003; 5: 615-27. https://doi.org/10.2165/00148581-200305090-00004
  18. Karaman S, Evren V, Firat V, Cankayali I. The effects of dexmedetomidine on spontaneous contractions of isolated gravid rat myometrium. Adv Ther 2006; 23: 238-43. https://doi.org/10.1007/BF02850129
  19. Sia AT, Kwek K, Yeo GS. The in vitro effects of clonidine and dexmedetomidine on human myometrium. Int J Obstet Anesth 2005; 14: 104-7. https://doi.org/10.1016/j.ijoa.2004.11.004
  20. Shin SH, You JC, Ahn JH, Kim YH, Yoon JU, Cho AR, et al. Anti-inflammatory effects of dexmedetomidine on human amnion-derived WISH cells. Int J Med Sci 2020; 17: 2496-504. https://doi.org/10.7150/ijms.49909
  21. Nadeau-Vallee M, Quiniou C, Palacios J, Hou X, Erfani A, Madaan A, et al. Novel noncompetitive IL-1 receptor-biased ligand prevents infection- and inflammation-induced preterm birth. J Immunol 2015; 195: 3402-15. https://doi.org/10.4049/jimmunol.1500758
  22. Sadowsky DW, Novy MJ, Witkin SS, Gravett MG. Dexamethasone or interleukin-10 blocks interleukin-1beta-induced uterine contractions in pregnant rhesus monkeys. Am J Obstet Gynecol 2003; 188: 252-63. https://doi.org/10.1067/mob.2003.70
  23. Bartlett SR, Sawdy R, Mann GE. Induction of cyclooxygenase-2 expression in human myometrial smooth muscle cells by interleukin-1beta: involvement of p38 mitogen-activated protein kinase. J Physiol 1999; 520: 399-406. https://doi.org/10.1111/j.1469-7793.1999.00399.x
  24. Christiaens I, Zaragoza DB, Guilbert L, Robertson SA, Mitchell BF, Olson DM. Inflammatory processes in preterm and term parturition. J Reprod Immunol 2008; 79: 50-7. https://doi.org/10.1016/j.jri.2008.04.002
  25. Fortunato SJ, Menon R, Lombardi SJ. Role of tumor necrosis factor-alpha in the premature rupture of membranes and preterm labor pathways. Am J Obstet Gynecol 2002; 187: 1159-62. https://doi.org/10.1067/mob.2002.127457
  26. 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: 1660-7. https://doi.org/10.1016/0002-9378(94)90418-9
  27. Xu L, Bao H, Si Y, Wang X. Effects of dexmedetomidine on early and late cytokines during polymicrobial sepsis in mice. Inflamm Res 2013; 62: 507-14. https://doi.org/10.1007/s00011-013-0604-5
  28. Chen R, Kang Z, Wang Y, Zhao J, Li S. The anti-inflammatory effect of dexmedetomidine administration on patients undergoing intestinal surgery: a randomized study. Drugs R D 2021; 21: 445-53. https://doi.org/10.1007/s40268-021-00368-x
  29. Ohta Y, Miyamoto K, Kawazoe Y, Yamamura H, Morimoto T. Effect of dexmedetomidine on inflammation in patients with sepsis requiring mechanical ventilation: a sub-analysis of a multicenter randomized clinical trial. Crit Care 2020; 24: 493-8. https://doi.org/10.1186/s13054-020-03207-8
  30. Sia AT, Kwek K, Yeo GS. The in vitro effects of clonidine and dexmedetomidine on human myometrium. Int J Obstet Anesth 2005; 14: 104-7. https://doi.org/10.1016/j.ijoa.2004.11.004
  31. Karaman S, Evren V, Firat V, Cankayali I. The effects of dexmedetomidine on spontaneous contractions of isolated gravid rat myometrium. Adv Ther 2006; 23: 238-43. https://doi.org/10.1007/BF02850129
  32. Min KJ, Lee JT, Joe EH, Kwon TK. An IκBα phosphorylation inhibitor induces heme oxygenase-1 (HO-1) expression through the activation of reactive oxygen species (ROS)-Nrf2-ARE signaling and ROS-PI3K/Akt signaling in an NF-κB-independent mechanism. Cell Signal 2011; 23: 1505-13. https://doi.org/10.1016/j.cellsig.2011.05.013
  33. Lim S, MacIntyre DA, Lee YS, Khanjani S, Terzidou V, Teoh TG, et al. Nuclear factor kappa B activation occurs in the amnion prior to labour onset and modulates the expression of numerous labour associated genes. PLoS One 2012; 7: e34707. https://doi.org/10.1371/journal.pone.0034707
  34. Kumar S, Boehm J, Lee JC. p38 MAP kinases: key signalling molecules as therapeutic targets for inflammatory diseases. Nat Rev Drug Discov 2003; 2: 717-26. https://doi.org/10.1038/nrd1177
  35. Bhat NR, Feinstein DL, Shen Q, Bhat AN. p38 MAPK-mediated transcriptional activation of inducible nitric-oxide synthase in glial cells. Roles of nuclear factors, nuclear factor kappa B, cAMP response element-binding protein, CCAAT/enhancer-binding protein-beta, and activating transcription factor-2. J Biol Chem 2002; 277: 29584-92. https://doi.org/10.1074/jbc.M204994200
  36. Vanden Berghe W, Plaisance S, Boone E, De Bosscher K, Schmitz ML, Fiers W, et al. p38 and extracellular signal-regulated kinase mitogen-activated protein kinase pathways are required for nuclear factor-kappaB p65 transactivation mediated by tumor necrosis factor. J Biol Chem 1998; 273: 3285-90. https://doi.org/10.1074/jbc.273.6.3285