Burn-induced thymic apoptosis corresponds with altered TGF-beta(1) and Smad 2/3.
Immune suppression is a common complication of injury. Transforming growth factor-beta(1) (TGF-beta(1)), 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-beta(1). We hypothesized that burn-induced immunosuppression would be accompanied by increased apoptosis in lymphoid organs, a change likely associated with changes in TGF-beta(1) 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-beta(1) 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-beta(1) 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-beta(1) 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-beta(1) and Smad 2/3 counterregulation in response to injury may represent a potential mechanism for postinjury immune suppression.
Hobson
Kristina G
KG
Department of Surgery, University of California Davis, 95616, USA.
Cho
Kiho
K
Adamson
Lee K
LK
Greenhalgh
David G
DG
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D002056:Burns / Q000276:immunology* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D051899:Smad2 Protein; D051900:Smad3 Protein; D013950:Thymus Gland / Q000737:chemistry / Q000473:pathology* / Q000502:physiology; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000032:analysis*; D053773:Transforming Growth Factor beta1
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; C508961:Tgfb1 protein, mouse; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1