Stat6 null phenotype human lymphocytes exhibit increased apoptosis

Eva Galka, Jennifer Lynn Thompson, Wen Jie Zhang, Lisa S. Poritz, Walter A. Koltun

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Inflammatory bowel disease (IBD) is associated with altered apoptosis and increased levels of Th1 cytokines (IL-12, TNF-α, and IFN-γ). These proinflammatory events may result from dysfunctional IL-4/Stat6 signal transduction that normally promotes Th2 lymphocyte differentiation and consequential down-regulation of the immune response. The goal of the present study was to measure apoptosis, levels of relevant cytokines, and the effects of cytokine manipulation on apoptosis in cell lines derived from IBD patients that express dysfunctional Stat6 (Stat6 null phenotype) and wild-type Stat6 (Stat6 high phenotype). Lymphocytes with Stat6 null phenotype (n = 5) or wild-type (n = 5) status were cultured with and without the addition of exogenous cytokines or neutralizing antibodies (IL-12, TNF-α, and IFN-γ). Apoptosis was determined by flow cytometry using Annexin V-PE dual staining. Cytokine levels were determined by ELISA. Stat6 null phenotype cells exhibited increased apoptosis compared with wild-type cell lines (13.3% ± 2.9 versus 4.5% ± 0.4, P < 0.0001). Four of five Stat6 null phenotype cell lines expressed 5- to 10-fold elevations in IL-12 and IFN-γ. Addition of exogenous cytokines or neutralizing antibodies had no effect on apoptosis. Apoptotic cell death is elevated in Stat6 null phenotype cell lines suggesting a role for Stat6 in apoptosis regulation, a previously unrecognized observation. Increased levels of IL-12 and IFN-γ were found in the Stat6 null phenotype cell lines; however, the apoptosis observed is not the consequence of increased IL-12, IFN-γ, or TNF-α. Stat6 null phenotype cell lines exhibit variably increased levels of these Th1 cytokines, consistent with their human source, and may be a valid source for investigations into IBD pathophysiology.

Original languageEnglish (US)
Pages (from-to)14-20
Number of pages7
JournalJournal of Surgical Research
Issue number1
StatePublished - Nov 2004

All Science Journal Classification (ASJC) codes

  • Surgery


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