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Ontogeny of Toll Like Receptor 2 in the Developing Rat Lung
Author(s) -
Benjamin John T,
Chaplain Jennifer,
Bochkareva Aleksandra,
Gebb Sarah
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.899.4
Subject(s) - tlr2 , bronchopulmonary dysplasia , lung , fetus , receptor , andrology , toll like receptor , biology , innate immune system , immunology , immune system , mesenchymal stem cell , medicine , pregnancy , pathology , gestational age , genetics
Background: Antenatal bacterial colonization and subsequent inflammation of the fetal membranes increases the risk of Bronchopulmonary Dysplasia (BPD), a disease associated with recruitment of various inflammatory cells to the lung. Innate immune signaling through Toll like receptor 2 (TLR2) is used by various pathogens causing antenatal infections. An increase in TLR2 postnatally may thus provide a molecular mechanism by which antenatal bacterial colonization causes subsequent preterm lung disease. Objective: We hypothesized that TLR2 expression increases postnatally in the developing lung, in part because of changes in the oxygen environment. To test this we used a rat model of fetal lung development. Methods: Lungs isolated from embryonic (E) day 15, 16, 18, 20 and postnatal (P) day 2 and 4 rats were used to quantify TLR2 gene expression. For invitro studies, E15 lung explants and mesenchymal cells were isolated and cultured in 21% (postnatal) O 2 or 3% (fetal) O 2 . TLR2 gene expression was measured by RT‐PCR. Results: Lung TLR2 expression increased 700% from E15 to P4 ( P < 0.05). Almost half of this increase (300%) occurred in the first 2 days after birth. There was a trend towards increased expression of TLR2 in both explants (243% increase; P = 0.06) and isolated lung mesenchymal cells (244% increase; P = 0.08) cultured in 21% O 2 Vs 3% O 2 . Conclusion: These data suggests that TLR2 gene expression increases in the immediate postnatal period. This postnatal increase may be mediated in part by changes in oxygen environment after birth. In the presence of antenatal bacterial colonization, increased TLR2 postnatally could lead to increased inflammation and subsequent chronic lung injury.