Toll-like receptors and agonist responses in the developing fetal sheep lung

Noah Hillman, Timothy Moss, Ilias Nitsos, Boris Kramer, Cindy Bachurski, Machiko Ikegami, Alan Jobe, Suhas Kallapur

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Toll-like receptors (TLRs) are pattern recognition molecules that initiate innate immune responses. Intra-amniotic exposure of fetal sheep to pro-inflammatory stimuli causes pulmonary inflammation and induced lung maturation. We examined TLR ontogeny and fetal lung responsiveness to three different TLR agonists. We cloned ovine TLRs 2, 3, and 4 and found 83-88 homology between these ovine and human TLRs. Lung TLR2 and 4 mRNAs increased throughout late gestation to 50 of adult level in the term newborn lamb. Doses of 10 mg of PAMCysK4 (TLR2 agonist), poly I:C dsRNA (TLR3 agonist), or E. coli O55:B5 lipopoysaccharide (LPS) (TLR4 agonist) were given by intra-amniotic injection 2 d or 7 d before operative delivery of preterm lambs at 123 d (n = 4-7/group). The TLR4 agonist induced lung inflammation and maturation, whereas the TLR2 agonist gave less consistent responses. Intra-amniotic LPS increased TLR2 mRNA expression primarily in the inflammatory cells and TLR4 mRNA diffusely in multiple cell types. The TLR3 agonist had no effects, and TLR3 mRNA in the fetal lung did not change after LPS exposure. We conclude that TLR2 and TLR4 mRNAs increase through gestation and expression of TLR2 and TLR4 are induced by LPS in the fetal sheep lung.
Original languageEnglish
Pages (from-to)388 - 393
Number of pages6
JournalPediatric Research
Volume63
Issue number4
DOIs
Publication statusPublished - 2008
Externally publishedYes

Cite this

Hillman, N., Moss, T., Nitsos, I., Kramer, B., Bachurski, C., Ikegami, M., ... Kallapur, S. (2008). Toll-like receptors and agonist responses in the developing fetal sheep lung. Pediatric Research, 63(4), 388 - 393. https://doi.org/10.1203/PDR.0b013e3181647b3a
Hillman, Noah ; Moss, Timothy ; Nitsos, Ilias ; Kramer, Boris ; Bachurski, Cindy ; Ikegami, Machiko ; Jobe, Alan ; Kallapur, Suhas. / Toll-like receptors and agonist responses in the developing fetal sheep lung. In: Pediatric Research. 2008 ; Vol. 63, No. 4. pp. 388 - 393.
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abstract = "Toll-like receptors (TLRs) are pattern recognition molecules that initiate innate immune responses. Intra-amniotic exposure of fetal sheep to pro-inflammatory stimuli causes pulmonary inflammation and induced lung maturation. We examined TLR ontogeny and fetal lung responsiveness to three different TLR agonists. We cloned ovine TLRs 2, 3, and 4 and found 83-88 homology between these ovine and human TLRs. Lung TLR2 and 4 mRNAs increased throughout late gestation to 50 of adult level in the term newborn lamb. Doses of 10 mg of PAMCysK4 (TLR2 agonist), poly I:C dsRNA (TLR3 agonist), or E. coli O55:B5 lipopoysaccharide (LPS) (TLR4 agonist) were given by intra-amniotic injection 2 d or 7 d before operative delivery of preterm lambs at 123 d (n = 4-7/group). The TLR4 agonist induced lung inflammation and maturation, whereas the TLR2 agonist gave less consistent responses. Intra-amniotic LPS increased TLR2 mRNA expression primarily in the inflammatory cells and TLR4 mRNA diffusely in multiple cell types. The TLR3 agonist had no effects, and TLR3 mRNA in the fetal lung did not change after LPS exposure. We conclude that TLR2 and TLR4 mRNAs increase through gestation and expression of TLR2 and TLR4 are induced by LPS in the fetal sheep lung.",
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Hillman, N, Moss, T, Nitsos, I, Kramer, B, Bachurski, C, Ikegami, M, Jobe, A & Kallapur, S 2008, 'Toll-like receptors and agonist responses in the developing fetal sheep lung', Pediatric Research, vol. 63, no. 4, pp. 388 - 393. https://doi.org/10.1203/PDR.0b013e3181647b3a

Toll-like receptors and agonist responses in the developing fetal sheep lung. / Hillman, Noah; Moss, Timothy; Nitsos, Ilias; Kramer, Boris; Bachurski, Cindy; Ikegami, Machiko; Jobe, Alan; Kallapur, Suhas.

In: Pediatric Research, Vol. 63, No. 4, 2008, p. 388 - 393.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Toll-like receptors and agonist responses in the developing fetal sheep lung

AU - Hillman, Noah

AU - Moss, Timothy

AU - Nitsos, Ilias

AU - Kramer, Boris

AU - Bachurski, Cindy

AU - Ikegami, Machiko

AU - Jobe, Alan

AU - Kallapur, Suhas

PY - 2008

Y1 - 2008

N2 - Toll-like receptors (TLRs) are pattern recognition molecules that initiate innate immune responses. Intra-amniotic exposure of fetal sheep to pro-inflammatory stimuli causes pulmonary inflammation and induced lung maturation. We examined TLR ontogeny and fetal lung responsiveness to three different TLR agonists. We cloned ovine TLRs 2, 3, and 4 and found 83-88 homology between these ovine and human TLRs. Lung TLR2 and 4 mRNAs increased throughout late gestation to 50 of adult level in the term newborn lamb. Doses of 10 mg of PAMCysK4 (TLR2 agonist), poly I:C dsRNA (TLR3 agonist), or E. coli O55:B5 lipopoysaccharide (LPS) (TLR4 agonist) were given by intra-amniotic injection 2 d or 7 d before operative delivery of preterm lambs at 123 d (n = 4-7/group). The TLR4 agonist induced lung inflammation and maturation, whereas the TLR2 agonist gave less consistent responses. Intra-amniotic LPS increased TLR2 mRNA expression primarily in the inflammatory cells and TLR4 mRNA diffusely in multiple cell types. The TLR3 agonist had no effects, and TLR3 mRNA in the fetal lung did not change after LPS exposure. We conclude that TLR2 and TLR4 mRNAs increase through gestation and expression of TLR2 and TLR4 are induced by LPS in the fetal sheep lung.

AB - Toll-like receptors (TLRs) are pattern recognition molecules that initiate innate immune responses. Intra-amniotic exposure of fetal sheep to pro-inflammatory stimuli causes pulmonary inflammation and induced lung maturation. We examined TLR ontogeny and fetal lung responsiveness to three different TLR agonists. We cloned ovine TLRs 2, 3, and 4 and found 83-88 homology between these ovine and human TLRs. Lung TLR2 and 4 mRNAs increased throughout late gestation to 50 of adult level in the term newborn lamb. Doses of 10 mg of PAMCysK4 (TLR2 agonist), poly I:C dsRNA (TLR3 agonist), or E. coli O55:B5 lipopoysaccharide (LPS) (TLR4 agonist) were given by intra-amniotic injection 2 d or 7 d before operative delivery of preterm lambs at 123 d (n = 4-7/group). The TLR4 agonist induced lung inflammation and maturation, whereas the TLR2 agonist gave less consistent responses. Intra-amniotic LPS increased TLR2 mRNA expression primarily in the inflammatory cells and TLR4 mRNA diffusely in multiple cell types. The TLR3 agonist had no effects, and TLR3 mRNA in the fetal lung did not change after LPS exposure. We conclude that TLR2 and TLR4 mRNAs increase through gestation and expression of TLR2 and TLR4 are induced by LPS in the fetal sheep lung.

UR - http://www.ncbi.nlm.nih.gov/pubmed/18356744

U2 - 10.1203/PDR.0b013e3181647b3a

DO - 10.1203/PDR.0b013e3181647b3a

M3 - Article

VL - 63

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EP - 393

JO - Pediatric Research

JF - Pediatric Research

SN - 0031-3998

IS - 4

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