TRANSCRIPTIONAL AND TRANSLATIONAL REGULATION OF IL-1-ALPHA AND IL-1-BETA ACCOUNT FOR THE CONTROL OF IL-1 IN EXPERIMENTAL YERSINIOSIS

Interleukin 1 (IL-1) gene expression was investigated in mice followin g oral infection with Yersinia enterocolitica 08. In Peyer's patches ( PP), the primary site of bacterial invasion, induction of IL-1 alpha m RNA was delayed when compared to IL-1 beta mRNA. As shown by in situ h ybridization, IL-1 alpha and IL-1 beta mRNA were found to be expressed within different cell types. These results indicate that expression o f the two forms of IL-1 is regulated in a cell-specific manner at the transcriptional level. Moreover, IL-1 (alpha and beta) mRNA was increa sed in other organs such as spleen and lung. In spleens, IL-1 beta mRN A was found within the red pulp, and IL-1 alpha mRNA was located to th e marginal zone confirming that differential expression of IL-1 alpha and IL-1 beta mRNA does not represent a tissue-specific event. However , as revealed by immunohistochemistry and measuring IL-1 activity in t issue homogenates, synthesis of IL-1 proteins was not detectable in sp leens, unless mice were challenged with LPS. Because IL-1 synthesis wa s inducible in spleen cells following actinomycin D treatment, the res ults indicate that at distant sites of infection IL-1 (alpha and beta) mRNA is expressed but not translated into protein. It is concluded th at cell-specific transcription of IL-1 alpha and IL-1 beta as well as dissociation between IL-1 mRNA and protein synthesis are two mechanism s effective in regulating the production of IL-1 during infection.