POSTTRANSCRIPTIONAL LIPOPOLYSACCHARIDE REGULATION OF THE LYSOZYME GENE AT PROCESSING OF THE PRIMARY TRANSCRIPT IN MYELOMONOCYTIC HD11 CELLS

Lysozyme is increasingly expressed in macrophages in inflammatory resp onse to bacterial LPS. In this study, we investigated the mechanisms t hat control expression of the lysozyme gene in myelomonocytic HD11 cel ls activated by LPS, Nuclear run-on transcription assays showed that L PS caused a 15-fold increase in the transcription rate of the lysozyme gene. However, Northern analyses with lysozyme cDNA and intron sequen ces revealed that the LPS-induced increase in nuclear lysozyme transcr ipts greatly exceeded the increase in transcription rate. Furthermore, nuclear lysozyme transcripts in untreated cells with a t(1/2) of <10 min were more unstable than those accumulated in LPS-activated cells. We suggested, therefore, that the increased lysozyme expression follow ing LPS treatment was largely due to a nuclear stabilization of the pr imary transcript, Interestingly, the increase in stability of the lyso zyme primary transcript was accompanied by changes in nuclear processi ng including an increase in poly(A) tail length, which gradually short ened after entering the cytoplasm, The long lysozyme poly(A) tail, how ever, did not result in any increase in polysomal recruitment for tran slation or in stability of the cytoplasmic lysozyme mRNA.