The 3 ' untranslated region of tumor necrosis factor-alpha is highly conserved in idiopathic pulmonary fibrosis

Tumour necrosis factor alpha (TNF-alpha), a pro-inflammatory cytokine essen tial for the function of the immune system, has been implicated in the path ogenesis of idiopathic pulmonary fibrosis (IPF). Production of TNF-alpha is regulated at both the transcriptional and post-transcriptional levels by a number of factors including interleukin-10 (IL-10). We have shown that the re is significant TNF-alpha activity in patients with IPF, despite the pres ence of significant amounts of IL-10 and 11-10R, IL-10 is thought to influe nce the tight translational repression of TNF-alpha mRNA in pulmonary macro phages. The essential element in this regulation is the AU-rich element (AR E) present in the 3' untranslated region of TNF-alpha, We hypothesised that polymorphism in the 3' UTR region of TNF-alpha explains the apparent failu re of IL-10 to down regulate TNF-alpha in patients with IPF. Using single s trand conformation polymorphism (SSCP) analysis, we have screened this regi on in 96 patients with IPF; using nine sets of overlapping PCR primers. All samples were successfully amplified for each primer set, but SSCP analysis was unable to detect point mutations or polymorphisms in the patients in a ny of the nine fragments, Results from this study suggest that the 3' UTR r egion of TNF-alpha is highly conserved in IPF and mutation of this region i s unlikely to be involved in the pathogenesis of IPF.