Burn-induced thymic apoptosis corresponds with altered TGF-β1 and Smad 2/3

Kristina G. Hobson, Kiho Cho, Lee K. Adamson, David G Greenhalgh

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Immune suppression is a common complication of injury. Transforming growth factor-β1 (TGF-β1), a cytokine with diverse anti-inflammatory and anti-apoptotic effects, may play an important role. Smad 2 and Smad 3 are transcription factors that mediate the effects of TGF-β1. We hypothesized that burn-induced immunosuppression would be accompanied by increased apoptosis in lymphoid organs, a change likely associated with changes in TGF-β1 and Smad 2/3 expression. Mice were subjected to 18% body surface area flame burn. Lymph nodes, spleen, and thymus were harvested at multiple time points after injury. TGF-β1 and Smad 2/3 expression and levels of apoptosis were determined in whole tissue and in sorted T-cells by flow cytometry, RT-PCR, ELISA, and Western blot. TGF-β1 protein expression in the thymus increased from 1 to 7 days. Smad 2/3 protein expression was decreased at the same time points. This down-regulation was more dramatic in the non-T-cells than in the T-cells themselves. RT-PCR confirmed down-regulation of Smad 3 mRNA in the thymus from 3 to 6 h. Apoptosis in the thymus doubled at 1 day (6.4% control vs 12.8% burned), which corresponded with a marked decrease in thymus mass on subjective assessment. No changes were observed in other lymphoid organs. Burn injury in mice increases TGF-β1 expression in the thymus, while suppressing expression of its intracellular mediator, Smad 2/3. This response is most pronounced in the non-T-cell tissue, which suggests the thymic epithelial cells may be responsible for the increased thymic apoptosis. This TGF-β1 and Smad 2/3 counterregulation in response to injury may represent a potential mechanism for postinjury immune suppression.

Original languageEnglish (US)
Pages (from-to)4-9
Number of pages6
JournalJournal of Surgical Research
Volume105
Issue number1
DOIs
StatePublished - 2002

Keywords

  • Apoptosis
  • Burns
  • Immunosuppression
  • Smad
  • TGFβ

ASJC Scopus subject areas

  • Surgery

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