ABSTRACT
Interleukin 1 (IL-1) gene expression was investigated in mice following oral infection with Yersinia enterocolitica 08. In Peyer's patches (PP), the primary site of bacterial invasion, induction of IL-1 alpha mRNA was delayed when compared to IL-1 beta mRNA. As shown by in situ hybridization. IL-1 alpha and IL-1 beta mRNA were found to be expressed within different cell types. These results indicate that expression of 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 increased in other organs such as spleen and lung. In spleens, IL-1 beta mRNA was found within the red pulp, and IL-1 alpha mRNA was located to the 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 tissue homogenates, synthesis of IL-1 proteins was not detectable in spleens, unless mice were challenged with LPS. Because IL-1 synthesis was inducible in spleen cells following actinomycin D treatment, the results indicate that at distant sites of infection IL-1 (alpha and beta) mRNA is expressed but not translated into protein. It is concluded that cell-specific transcription of IL-1 alpha and IL-1 beta as well as dissociation between IL-1 mRNA and protein synthesis are two mechanisms effective in regulating the production of IL-1 during infection.
Subject(s)
Gene Expression Regulation , Interleukin-1/biosynthesis , Peyer's Patches/immunology , Yersinia Infections/immunology , Yersinia enterocolitica , Animals , Blotting, Northern , Dactinomycin/pharmacology , Female , Gene Expression Regulation/drug effects , Immunoenzyme Techniques , In Situ Hybridization , Kinetics , Liver/immunology , Lung/immunology , Lymphocytes/drug effects , Lymphocytes/immunology , Mice , Mice, Inbred BALB C , Organ Specificity , Protein Biosynthesis , RNA, Messenger/biosynthesis , Spleen/immunology , Transcription, Genetic/drug effects , Yersinia Infections/metabolismABSTRACT
Interleukin(IL-)-1 is the prototype of a proinflammatory cytokine, produced in response to infection and other forms of trauma. At low concentrations IL-1 brings about increases in a number of defense mechanisms, particularly immunologic and inflammatory responses. However, over- or continued production of IL-1, as seen for example during septic infection, significantly contributes to pathological reactions such as hemodynamic shock. Thus, it is not surprising that IL-1 activities are tightly regulated, most notably at the levels of transcription and secretion. Additional regulation is provided by the action of a protein, that blocks the binding of IL-1 to its receptors. This protein, termed IL-1-receptor antagonist (IL-1ra) has been cloned recently, and may provide the possibility of specific therapeutic measures.
Subject(s)
Infections/physiopathology , Interleukin-1/physiology , Animals , Bacterial Infections/physiopathology , Immunity, Cellular , Interleukin 1 Receptor Antagonist Protein , Receptors, Interleukin-1/physiology , Sialoglycoproteins/physiologyABSTRACT
In situ production of interleukin 1 alpha (IL-1 alpha) and IL-1 beta was investigated in Peyer's patches (PP) of mice undergoing an acute bacterial infection with Yersinia enterocolitica O8. Synthesis of IL-1 beta, as determined by immunohistochemistry, was found primarily in monocytes migrating into the inflamed PP. In comparison, synthesis of IL-1 alpha was temporarily delayed by at least 24 h and was only found in mature macrophages, which did not produce detectable levels of IL-1 beta. This indicates a transition from IL-1 beta to IL-1 alpha production during maturation of monocytes into inflammatory macrophages, and further emphasizes a dichotomy between IL-1 alpha and IL-1 beta.