title: The effect of low dose lipopolysaccharide on thyroid hormone-regulated actin cytoskeleton modulation and type 2 iodothyronine deiodinase activity in astrocytes.
abstract: Systemic infection/inflammation can severely interfere with brain development. Lipopolysaccharide (LPS) is a major cell wall component of gram-negative bacteria and commonly used to model the response by infections. Since perinatal exposure to LPS shows neurodevelopmental defects partly similar to those seen in perinatal hypothyroidism, we examined the effect of LPS on thyroxin (T4)-mediated signalings in astrocytes. Initially, C6 rat glioma-derived clonal cells were used, whose biological nature is similar to that of astrocytes. To measure the effects of LPS and T4, actin polymerization and D2 activity assays were carried out. LPS treatment (10 ng/mL) markedly induced actin depolymerization, whereas 10 nM T4 promoted actin polymerization. Furthermore, T4 partly rescued LPS-induced actin depolymerization. LPS treatment (10 ng/mL) increased D2 activity, whereas T4 (10 nM) suppressed this activity. T4 restored LPS-increased D2 activity at 10 nM. LPS-induced actin depolymerization and D2 activity were blocked by p38 MAP kinase inhibitor. Such effects were not seen in T4-mediated changes. Furthermore, similar results were found in the cerebellar primary astrocyte. These results indicate that, although LPS affects T4-regulated cellular events such as actin polymerization and D2 activity, which may induce neurodevelopmental defects similar to those in perinatal hypothyroidism, LPS signaling pathways are independent of T4 signaling pathways.
authors: Department of Integrative Physiology, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors: Ming
authors: M
authors: Xu
authors: Toshiharu
authors: T
authors: Iwasaki
authors: Noriaki
authors: N
authors: Shimokawa
authors: Elizabeth M
authors: EM
authors: Sajdel-Sulkowska
authors: Noriyuki
authors: N
authors: Koibuchi
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism*; D001483:Base Sequence; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D002999:Clone Cells; D007453:Iodide Peroxidase / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008969:Molecular Sequence Data; D058105:Polymerization; D051381:Rats; D017208:Rats, Wistar; D013963:Thyroid Hormones / Q000378:metabolism*; D013974:Thyroxine / Q000008:administration & dosage / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D007453:Iodide Peroxidase; D008070:Lipopolysaccharides; D013963:Thyroid Hormones; D013974:Thyroxine; D048051:p38 Mitogen-Activated Protein Kinases; D000097564:Iodothyronine Deiodinase Type II