The central MHC gene, BAT1, may encode a protein that down-regulates cytokine production

Background: BAT1 belongs to the DEAD-box family of RNA-binding proteins and is encoded in the central MHC. To determine whether it affects immune resp onses and hence diseases influenced by MHC haplotypes, U937, THP1 and Jurka t cells were stably transfected with anti-sense DNA corresponding to exons 2-5 of BAT1 using a retroviral vector. Results: Anti-sense transfectants carried anti-sense DNA and expressed anti -sense mRNA. After mitogenic stimulation, they produced higher levels of TN F alpha, IL-1 and IL-6 than equivalent cells carrying the vector alone, sug gesting that BAT1 may downregulate acute phase cytokine production. Polyclo nal antibodies raised against a peptide in exon 8 of BAT1 recognized approx imate to 50 kDa and approximate to 38 kDa proteins in all cell lines tested , including the anti-sense transfectants. Expression was localized to the n ucleolus in dividing fibroblasts. However the immunochemistry may be confou nded by a recently described gene, DDXL, on chromosome 19, which shares a 8 9% amino acid identity with BAT1. RT-PCR analyses established that BAT1 and DDXL mRNA are expressed in resting U937, THP1 and Jurkat cells. BAT1 and D DXL are divergent in the exons selected for the anti-sense study. Conclusions: BAT1 is a negative regulator of inflammation. Future studies s hould address how its functions relate to those of DDXL.