학술논문

Bone marrow cells produce a novel TSHβ splice variant that is upregulated in the thyroid following systemic virus infection.
Document Type
Article
Source
Genes & Immunity. Jan2009, Vol. 10 Issue 1, p18-26. 9p. 1 Chart, 4 Graphs.
Subject
*BONE marrow cells
*VIRUS diseases
*AUTOIMMUNE thyroiditis
*THYROTROPIN
*INTRONS
*AUTOIMMUNITY
*EXONS (Genetics)
*IMMUNE system
Language
ISSN
1466-4879
Abstract
Although cells of the immune system can produce thyroid-stimulating hormone (TSH), the significance of that remains unclear. Using 5′ rapid amplification of cDNA ends (RACE), we show that mouse bone marrow (BM) cells produce a novel in-frame TSHβ splice variant generated from a portion of intron 4 with all of the coding region of exon 5, but none of exon 4. The TSHβ splice variant gene was expressed at low levels in the pituitary, but at high levels in the BM and the thyroid, and the protein was secreted from transfected Chinese hamster ovary (CHO) cells. Immunoprecipitation identified an 8 kDa product in lysates of CHO cells transfected with the novel TSHβ construct, and a 17 kDa product in lysates of CHO cells transfected with the native TSHβ construct. The splice variant TSHβ protein elicited a cAMP response from FRTL-5 thyroid follicular cells and a mouse alveolar macrophage (AM) cell line. Expression of the TSHβ splice variant, but not the native form of TSHβ, was significantly upregulated in the thyroid during systemic virus infection. These studies characterize the first functional splice variant of TSHβ, which may contribute to the metabolic regulation during immunological stress, and may offer a new perspective for understanding autoimmune thyroiditis.Genes and Immunity (2009) 10, 18–26; doi:10.1038/gene.2008.69; published online 28 August 2008 [ABSTRACT FROM AUTHOR]