Background Behçet disease (BD) is manifested by recurrent acute iridocyclitis with hypopyon in the active phase, which regresses spontaneously. Hypopyon consists of inflammatory cells infiltrating the eye, with polymorphonuclear cells (PMNs) as the main component. The present study was conducted to investigate the apoptosis property of PMNs in BD patients with uveitis. Methods PMNs were purified from peripheral blood cells of BD patients with uveitis in the active or remission phase and were cultured for 12 hours. In some cultures, lipopolysaccharide (LPS), antagonistic anti-TNFα antibody, agonistic anti-Fas antibody, or Fas:Fc fusion protein was added. At the end of cultures, apoptotic cells were evaluated by Annexin V expression using flow cytometry. Results Spontaneous apoptosis of PMNs showed lower levels in the remission phase of BD-related uveitis compared with the active phase or healthy controls. The lower level of PMN apoptosis in the remission phase of uveitis in BD remained even by stimulation with LPS, anti-TNFα antibody, or Fas:Fc fusion protein, which was abolished in the presence of agonistic anti-Fas antibody. Conclusions In BD patients, the apoptosis of PMNs was reduced in the remission phase of uveitis and restored in the active phase, which arose from the apoptotic cell death in part via Fas-Fas ligand interaction.

Duchenne muscular dystrophy (DMD) is an X-linked lethal disorder caused by a defect in the DMD gene, which encodes the cytoskeletal protein dystrophin. Utrophin is an autosomal homolog of the DMD gene product dystrophin, and augmented expression of endogenous utrophin is expected to provide an alternative therapeutic approach to DMD. We previously reported that an immune response against a beta-galactosidase-expressing adenovirus vector, AxCALacZ, resulted in an accumulation of endogenous utrophin on the extrasynaptic sarcolemma in dystrophin-deficient mdx mice. To determine which cytokine is involved in the regulation of utrophin expression, we directly injected several cytokines separately into neonatal mdx muscles and tested whether the expression of utrophin is increased on the sarcolemma. Importantly, among the cytokines tested, solely interleukin 6 (IL-6) successfully increased expression of utrophin. Moreover, the increase in utrophin mRNA was detected in recombinant IL-6-injected mdx muscles by quantitative real-time reverse transcriptase-polymerase chain reaction. Further, IL-6 expression was elevated in AxCALacZ-infected mdx muscle at an early stage, and anti-IL-6 receptor (IL-6R) antibody treatment blocked enhanced utrophin expression in AxCALacZ-infected mdx muscle. We should point out, however, that overexpression of utrophin due to recombinant IL-6 treatment lasted only 1 week. In addition, expression of utrophin was not evident in normal C57BL/10 neonatal muscles injected with IL-6. Taken together, these results suggest that IL-6 can induce overexpression of utrophin on the extrasynaptic sarcolemma but requires preexisting factors in neonatal mdx muscle to fully regulate utrophin expression.

Our results clearly showed that the utrophin A promoter is not sufficient to drive expression in muscle, but other regulatory elements are required.