Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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Advances in Clinical and Experimental Medicine

2016, vol. 25, nr 5, September-October, p. 887–893

doi: 10.17219/acem/39940

Publication type: original article

Language: English

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Increased Expression of TLR4 and TLR7 but Not Prolactin mRNA by Peripheral Blood Monocytes in Active Celiac Disease

Iva Brynychova1,B,C,D,F, Iva Hoffmanova2,E,F, Milos Dvorak3,E,F, Pavlina Dankova1,A,C,E,F

1 Department of Anthropology and Human Genetics, Faculty of Science, Charles University in Prague, Czech Republic

2 Second Department of Internal Medicine, Third Faculty of Medicine, Charles University in Prague, Czech Republic

3 First Medical Faculty, Charles University in Prague and General University Hospital in Prague, Czech Republic

Abstract

Background. Celiac disease (CD) is an organ-specific autoimmune disease, and both adaptive and innate immunity are involved in its development.
Objectives. The aim of the study was to determine whether the markers of intestinal mucosal inflammation in CD can be detected in peripheral blood monocytes (PBMs), and whether the immune properties of PBMs change as the clinical signs and symptoms of CD improve after the introduction of a gluten-free diet (GFD). The focus was on changes in mRNA expression of selected toll-like receptors (TLR2, TLR4, TLR7), stress cytokine prolactin (PRL), and proand anti-inflammatory cytokines (TNF-α, IL-6, IL-12, IL-10) in PBMs.
Material and Methods. The study involved 20 CD patients diagnosed according to the European Society for Pediatric Gastroenterology, Hepatology and Nutrition criteria and Marsh criteria: 10 recently-diagnosed cases (rCD) and 10 on a GFD for a minimum of one year. The control group comprised 10 ageand sex-matched healthy volunteers. PBMs from peripheral blood specimens were separated using immunomagnetic CD14+ beads. Total RNA was isolated using a standard commercial kit. Cytokine and TLR mRNA levels were quantified by relative qPCR with PGK1 as a reference gene.
Results. Significantly higher expression of TLR4 and TLR7 mRNA was observed in PBMs from rCD patients compared to the healthy controls (1.63 times higher; p < 0.05). TLR7 mRNA levels in rCDs were also significantly elevated in comparison to the CD-GFD patients (2.11 times higher; p < 0.01). TNF-α mRNA expression tended to be higher in both groups of patients; by contrast, in IL-6 mRNA, a trend to a fourfold decrease was detected in PBMs from the CD-GFD subjects. IL-10, IL-12 and PRL levels did not differ among the groups.
Conclusion. The data suggest that the inflammatory process in rCD intestinal mucosa and submucosa reflecting enterocyte damage can be detected in PBMs in peripheral blood. Further, the cytokine and TLR expression profile in PBMs alters after one year of GFD treatment.

Key words

celiac disease, monocytes, cytokines, prolactin, innate immunity

References (33)

  1. Mustalahti K, Catassi C, Reunanen A, Fabiani E, Heier M, McMillan S, Murray L, Metzger MH, Gasparin M, Bravi E, Maki M: The prevalence of celiac disease in Europe: Results of a centralized, international mass screening project. Ann Med 2010, 42, 587–595.
  2. Forsberg G, Fahlgren A, Horstedt P, Hammarstrom S, Hernell O, Hammarstrom ML: Presence of bacteria and innate immunity of intestinal epithelium in childhood celiac disease. Am J Gastroenterol 2004, 99, 894–904.
  3. Akashi-Takamura S, Miyake K: Toll-like receptors (TLRs) and immune disorders. J Infect Chemother 2006, 12, 233–240.
  4. Stene LC, Honeyman MC, Hoffenberg EJ, Haas JE, Sokol RJ, Emery L, Taki I, Norris JM, Erlich HA, Eisenbarth GS, Rewers M: Rotavirus infection frequency and risk of celiac disease autoimmunity in early childhood: A longitudinal study. Am J Gastroenterol 2006, 10, 2333–2340.
  5. Deane JA, Pisitkun P, Barrett RS, Feigenbaum L, Town T, Ward JM, Flavell RA, Bolland S: Control of toll-like receptor 7 expression is essential to restrict autoimmunity and dendritic cell proliferation. Immunity 2007, 27, 801–810.
  6. Szebeni B, Veres G, Dezsofi A, Rusai K, Vannay A, Bokodi G, Vasarhelyi B, Korponay-Szabo IR, Tulassay TT, Arato A: Increased mucosal expression of toll-like receptor (TLR)2 and TLR4 in coeliac disease. J Pediatr Gastroenterol Nutr 2007, 45, 187–193.
  7. De Bellis A, Bizzarro A, Pivonello R, Lombardi G, Bellastella A: Prolactin and autoimmunity. Pituitary 2005, 8, 25–30.
  8. Orbach H, Shoenfeld Y: Hyperprolactinemia and autoimmune diseases. Autoimmun Rev 2007, 6, 537–542.
  9. Matalka KZ: Prolactin enhances production of interferon-gamma, interleukin-12, and interleukin-10, but not of tumor necrosis factor-alpha, in a stimulus-specific manner. Cytokine 2003, 21, 187–194.
  10. Kapur G, Patwari AK, Narayan S, Anand VK: Serum prolactin in celiac disease. J Trop Pediatr 2004, 50, 37–40.
  11. Felmet KA, Hall MW, Clark RSB, Jaffe R, Carcillo JA: Prolonged lymphopenia, lymphoid depletion, and hypoprolactinemia in children with nosocomial sepis and multiple organ failure. J Immunol 2005, 174, 3765–3772.
  12. Cejkova P, Cerna M, Markova M, Marek J, Lacinova Z, Haluzik M: Monitoring of the course of sepsis in hematooncological patients by extrapituitary prolactin expression in peripheral blood monocytes. Physiol Res 2012, 61, 481–488.
  13. Husby S, Koletzko S, Korponay-Szabo IR: European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 2012, 54, 572–573.
  14. Marsh MN: Gluten, major histocompatibility complex, and the small intestine. A molecular and immunological approach to the spectrum of gluten sensitivity (celiac sprue). Gastroenterology 1992, 102, 330–354.
  15. Eiro N, Gonzalez-Reyes S, Gonzalez L, Gonzalez LO, Altadill A, Andicoechea A, Fresno-Forcelledo MF, Rodrigo-Saez L, Vizoso FJ: Duodenal expression of toll-like receptors and interleukins are increased in both children and adult celiac patients. Dig Dis Sci 2012, 57, 2278–2285.
  16. Sapone A, Lammers KM, Casolaro V, Cammarota M, Giuliano MT, De Rosa M, Stefanile R, Mazzarella G, Tolone C, Russo MI, Esposito P, Ferraraccio F, Carteni M, Riegler G, de Magistris L, Fasano A: Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: Celiac disease and gluten sensitivity. BMC Med 2011, 9, 23.
  17. Cseh A, Vasarhelyi B, Szalay B, Molnar K, Nagy-Szakal D, Treszl A, Vannay A, Arato A, Tulassay T, Veres G: Immune phenotype of children with newly diagnosed and gluten-free diet-treated celiac disease. Dig Dis Sci 2011, 56, 792–798.
  18. Palova-Jelinkova L, Danova K, Drasarova H, Dvorak M, Funda DP, Fundova P, Kotrbova-Kozak A, Cerna M, Kamanova J, Martin SF, Freudenberg M, Tuckova L: Pepsin digest of wheat gliadin fraction increases production of IL-1 beta via TLR4/MyD88/TRIF/MAPK/NF-kappa B signaling pathway and an NLRP3 inflammasome activation. PLoS One 2013, 8.
  19. Dubois PCA, Trynka G, Franke L, Hunt KA, Romanos J, Curtotti A, Zhernakova A, Heap GAR, Adany R, Aromaa A, Bardella MT, van den Berg LH, Bockett NA, de la Concha EG, Dema B, Fehrmann RSN, FernandezArquero M, Fiatal S, Grandone E, Green PM, Groen HJM, Gwilliam R, Houwen RHJ, Hunt SE, Kaukinen K, Kelleher D, Korponay-Szabo I, Kurppa K, MacMathuna P, Maki M, Mazzilli MC, McCann OT, Mearin ML, Mein CA, Mirza MM, Mistry V, Mora B, Morley KI, Mulder CJ, Murray JA, Nunez C, Oosterom E, Ophoff RA, Polanco I, Peltonen L, Platteel M, Rybak A, Salomaa V, Schweizer JJ, Sperandeo MP, Tack GJ, Turner G, Veldink JH, Verbeek WHM, Weersma RK, Wolters VM, Urcelay E, Cukrowska B, Greco L, Neuhausen SL, McManus
  20. Cros J, Cagnard N, Woollard K, Patey N, Zhang SY, Senechal B, Puel A, Biswas SK, Moshous D, Picard C, Jais JP, D’Cruz D, Casanova JL, Trouillet C, Geissmann F: Human CD14(dim) monocytes patrol and sense nucleic acids and viruses via TLR7 and TLR8 receptors. Immunity 2010, 33, 375–386.
  21. Hoffmanova I, Sanchez D, Habova V, Andel M, Tuckova L, Tlaskalova-Hogenova H: Serological markers of enterocyte damage and apoptosis in patients with celiac disease, autoimmune diabetes mellitus and diabetes mellitus type 2. Physiol Res 2015, 64, 537–546.
  22. Cinova J, Palova-Jelinkova L, Smythies LE, Cerna M, Pecharova B, Dvorak M, Fruhauf P, Tlaskalova-Hogenova H, Smith PD, Tuckova L: Gliadin peptides activate blood monocytes from patients with celiac disease. J Clin Immunol 2007, 27, 201–209.
  23. Caruso R, Marafini I, Sedda S, Del Vecchio Blanco G, Giuffrida P, MacDonald TT, Corazza GR, Pallone F, Sabatino A, Monteleone G: Analysis of the cytokine profile in the duodenal mucosa of refractory coeliac disease patients. Clin Sci 2014, 126, 451–458.
  24. Kapoor A, Patwari AK, Kumar P, Jain A, Narayan S: Serum soluble interleukin-2 receptor, interleukin-6 and tumor necrosis factor alpha as markers of celiac disease activity. Indian J Pediatr 2013, 80, 108–113.
  25. Manavalan JS, Hernandez L, Shah JG, Konikkara J, Naiyer AJ, Lee AR, Ciaccio E, Minaya MT, Green PHR, Bhagat G: Serum cytokine elevations in celiac disease: Association with disease presentation. Hum Immunol 2010, 71, 50–57.
  26. Lahat N, Shapiro S, Karban A, Gerstein R, Kinarty A, Lerner A: Cytokine profile in coeliac disease. Scand J Immunol 1999, 49, 441–446.
  27. Bijjiga E, Martino AT: Interleukin 10 (IL-10) Regulatory cytokine and its clinical consequences. J Clin Cell Immol 2013, S1, 1–6.
  28. Torres MI, Casado MAL, Rios A: New aspects in celiac disease. World J Gastroenterol 2007, 13, 1156–1161.
  29. Liu TF, Jones BM: Impaired production of IL-12 in systemic lupus erythematosus. I. Excessive production of IL-10 suppresses production of IL-12 by monocytes. Cytokine 1998, 10, 140–147.
  30. Delvecchio M, Faienza MF, Lonero A, Rutigliano V, Francavilla R, Cavallo L: Prolactin may be increased in newly diagnosed celiac children and adolescents and decreases after 6 months of gluten-free diet. Horm Res Paediatr 2014, 81, 309–313.
  31. Varkonyi A, Boda M, Endreffy E, Nemeth I, Timar E: Coeliac disease: Always something to discover. Scand J Gastroenterol 1998, 33, 122–129.
  32. Beitnes ACR, Raki M, Brottveit M, Lundin KEA, Jahnsen FL, Sollid LM: Rapid accumulation of CD14(+) CD11c(+) dendritic cells in gut mucosa of celiac disease after in vivo gluten challenge. PLoS One 2012, 7.
  33. Ben-Jonathan N, LaPensee CR, LaPensee EW: What can we learn from rodents about prolactin in humans? Endocr Rev 2008, 29, 1–41.
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