NF-kappaB p65 subunit mediates lipopolysaccharide-induced Na(+)/I(-) symporter gene expression by involving functional interaction with the paired domain transcription factor Pax8

NICOLA JP; NAZAR M; MASCANFRONI ID; PELLIZAS CG; MASINI-REPISO AM

ENDOCRINE SOC

Año: 2010 vol. 24 p. 1846 - 1846

p>The Gram-negative bacterial endotoxin lipopolysaccharide (LPS) elicits a variety of biological responses. Na(+)/I(-) symporter (NIS)-mediated iodide uptake is the main rate-limiting step in thyroid hormonogenesis. We have recently reported that LPS stimulates TSH-induced iodide uptake. Here, we further analyzed the molecular mechanism involved in the LPS-induced NIS expression in Fisher rat thyroid cell line 5 (FRTL-5) thyroid cells. We observed an increase in TSH-induced NIS mRNA expression in a dose-dependent manner upon LPS treatment. LPS enhanced the TSH-stimulated NIS promoter activity denoting the NIS-upstream enhancer region (NUE) as responsible for the stimulatory effects. We characterized a novel putative conserved kappaB site for the transcription factor nuclear factor-kappaB (NF-kappaB) within the NUE region. NUE contains two binding sites for the transcription factor paired box 8 (Pax8), main regulator of NIS transcription. A physical interaction was observed between the