Abstract
Toll-like receptors (TLRs) are critical components of the innate immune system, acting as pattern recognition molecules and triggering an inflammatory response. TLR associated gene products are of interest in modulating inflammatory-related pulmonary diseases of the neonate. The ontogeny of TLR-related genes in human fetal lung has not been previously described and could elucidate additional functions and identify strategies for attenuating the effects of fetal inflammation. We examined the expression of 84 TLR-related genes on 23 human fetal lung samples from three groups with estimated ages of 60 (57–59 d), 90 (89–91 d), and 130 (117–154 d) d. By using a false detection rate algorithm, we identified 32 genes displaying developmental regulation with TLR2 having the greatest up-regulation of TLR genes (9.2-fold increase) and TLR4 unchanged. We confirmed the TLR2 up-regulation by examining an additional 133 fetal lung tissue samples with a fluorogenic polymerase chain reaction assay (TaqMan) and found an exponential best-fit curve during the study time. The best-fit curve predicts a 6.1-fold increase from 60 to 130 d. We conclude that TLR2 is developmentally expressed from the early pseudoglandular stage of lung development to the canalicular stage.
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Abbreviations
- ACTB:
-
beta actin
- C t :
-
cycle threshold
- TLR:
-
toll-like receptor
References
Fusunyan RD, Nanthakumar NN, Baldeon ME, Walker WA 2001 Evidence for an innate immune response in the immature human intestine: toll-like receptors on fetal enterocytes. Pediatr Res 49: 589–593
Basu S, Fenton MJ 2004 Toll-like receptors: function and roles in lung disease. Am J Physiol Lung Cell Mol Physiol 286: L887–L892
Chaudhuri N, Whyte MK, Sabroe I 2007 Reducing the toll of inflammatory lung disease. Chest 131: 1550–1556
Raymond T, Schaller M, Hogaboam CM, Lukacs NW, Rochford R, Kunkel SL 2007 Toll-like receptors, Notch ligands and cytokines drive the chronicity of lung inflammation. Proc Am Thorac Soc 4: 635–641
Krediet TG, Wiertsema SP, Vossers MJ, Hoeks S, Fleer A, Ruven H, Rijkers GT 2007 Toll-like receptor 2 polymorphism is associated with preterm birth. Pediatr Res 62: 474–476
Abreu MT, Arditi M 2004 Innate immunity and Toll-like receptors: clinical implications of basic science research. J Pediatr 144: 421–429
Sadeghi K, Berger A, Langgartner M, Prusa A, Hayde M, Herkner K, Pollak A, Spittler A, Forster-Waldl E 2007 Immaturity of infection control in preterm and term newborns is associated with impaired toll-like receptor signaling. J Infect Dis 195: 296–302
Viemann D, Dubbel G, Schleifenbaum S, Harms E, Sorg C, Roth J 2005 Expression of toll-like receptors in neonatal sepsis. Pediatr Res 58: 654–659
Noakes PS, Hale J, Thomas R, Lane C, Devadason SG, Prescott SL 2006 Maternal smoking is associated with impaired neonatal toll-like-receptor-mediated immune responses. Eur Respir J 28: 721–729
Fleer A, Krediet TG 2007 Innate immunity: toll-like receptors and some more. Neonatology 92: 145–157
Willet KE, Jobe AH, Ikegami M, Newnham J, Brennan S, Sly PD 2000 Antenatal endotoxin and glucocorticoid effects on lung morphometry in preterm lambs. Pediatr Res 48: 782–788
Harju K, Glumoff V, Hallman M 2001 Ontogeny of toll-like receptors Tlr2 and Tlr4 in mice. Pediatr Res 49: 81–83
Hillman NH, Moss TJ, Nitsos I, Kramer BW, Bachurski CJ, Ikegami M, Jobe AH, Kallapur S 2008 Toll-like receptors and agonist responses in the developing fetal sheep lung. Pediatr Res 63: 388–393
Zhang X, Shan P, Jiang G, Cohn L, Lee PJ 2006 Toll-like receptor 4 deficiency causes pulmonary emphysema. J Clin Invest 116: 3050–3059
Jagannathan M, Hasturk H, Liang Y, Shin H, Hetzel JT, Kantarci A, Rubin D, McDonell ME, VanDyke TE, Ganley-Leal LM, Nikolajczyk BS 2009 TLR cross-talk specifically regulates cytokine production by B cells from chronic inflammatory disease patients. J Immunol 183: 7461–7470
Eskan MA, Hajishengallis G, Kinane DF 2007 Differential activation of human gingival epithelial cells and monocytes by Porphyromona gingivalis fimbriae. Infect Immun 75: 892–898
Chowdhury P, Sacks SH, Sheerin NS 2006 Toll-like receptors TLR2 and TLR4 initiate the innate immune response of the renal tubular epithelium to bacterial products. Clin Exp Immunol 145: 346–356
Ma Y, Li J, Chiu I, Wang Y, Sloane JA, Lu J, Kosaras B, Sidman RL, Volpe JJ, Vartanian T 2006 Toll-like receptor 8 functions as a negative regulator of neurite outgrowth and inducer of neuronal apoptosis. J Cell Biol 175: 209–215
Martin TR, Frevert CW 2005 Innate immunity in the lungs. Proc Am Thorac Soc 2: 403–411
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We thank Drs. Howard Kilbride and Jason Newland for critical reading of this article.
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Supported, in part, by the Center for Infant Pulmonary Disorders, Children's Mercy Hospital and Clinics, grant NHLBI R01 HL 70560 (W.E.T.), and Children's Mercy Hospital Research Vision. The project entitled “Laboratory of Developmental Biology” was supported by grant NIH Award Number 5R24HD000836 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
The content does not necessarily represent the official views of the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health.
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Petrikin, J., Gaedigk, R., Leeder, J. et al. Selective Toll-Like Receptor Expression in Human Fetal Lung. Pediatr Res 68, 335–338 (2010). https://doi.org/10.1203/PDR.0b013e3181ed1134
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DOI: https://doi.org/10.1203/PDR.0b013e3181ed1134
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