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. 1994 Sep;94(3):1328–1332. doi: 10.1172/JCI117452

Interleukin 1 is released by murine macrophages during apoptosis induced by Shigella flexneri.

A Zychlinsky 1, C Fitting 1, J M Cavaillon 1, P J Sansonetti 1
PMCID: PMC295219  PMID: 8083373

Abstract

Peritoneal macrophages undergoing apoptosis induced by Shigella flexneri infection release the inflammatory cytokine interleukin 1 (IL-1), but not IL-6 or tumor necrosis factor alpha (TNF alpha). Wild type shigella causes a very fast and significant release of IL-1 from prestimulated peritoneal macrophages, before the cell's integrity is compromised. Both IL-1 alpha and IL-1 beta are released, IL-1 beta in its mature processed form. IL-1 is released from presynthesized cytoplasmic pools. These results demonstrate that bacteria-induced apoptosis of macrophages may play an active role in vivo by releasing IL-1, which in turn mediates an early inflammatory response in epithelial tissues.

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Selected References

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  1. Cavaillon J. M., Fitting C., Haeffner-Cavaillon N., Kirsch S. J., Warren H. S. Cytokine response by monocytes and macrophages to free and lipoprotein-bound lipopolysaccharide. Infect Immun. 1990 Jul;58(7):2375–2382. doi: 10.1128/iai.58.7.2375-2382.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Haeffner-Cavaillon N., Cavaillon J. M., Moreau M., Szabó L. Interleukin 1 secretion by human monocytes stimulated by the isolated polysaccharide region of the Bordetella pertussis endotoxin. Mol Immunol. 1984 May;21(5):389–395. doi: 10.1016/0161-5890(84)90036-1. [DOI] [PubMed] [Google Scholar]
  3. Harvey J., Jones D. B. Human mucosal T-lymphocyte and macrophage subpopulations in normal and inflamed intestine. Clin Exp Allergy. 1991 Sep;21(5):549–560. doi: 10.1111/j.1365-2222.1991.tb00846.x. [DOI] [PubMed] [Google Scholar]
  4. Hogquist K. A., Nett M. A., Unanue E. R., Chaplin D. D. Interleukin 1 is processed and released during apoptosis. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8485–8489. doi: 10.1073/pnas.88.19.8485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Khelef N., Zychlinsky A., Guiso N. Bordetella pertussis induces apoptosis in macrophages: role of adenylate cyclase-hemolysin. Infect Immun. 1993 Oct;61(10):4064–4071. doi: 10.1128/iai.61.10.4064-4071.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kobayashi Y., Yamamoto K., Saido T., Kawasaki H., Oppenheim J. J., Matsushima K. Identification of calcium-activated neutral protease as a processing enzyme of human interleukin 1 alpha. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5548–5552. doi: 10.1073/pnas.87.14.5548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Mahida Y. R., Patel S., Gionchetti P., Vaux D., Jewell D. P. Macrophage subpopulations in lamina propria of normal and inflamed colon and terminal ileum. Gut. 1989 Jun;30(6):826–834. doi: 10.1136/gut.30.6.826. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Mahida Y. R., Wu K., Jewell D. P. Enhanced production of interleukin 1-beta by mononuclear cells isolated from mucosa with active ulcerative colitis of Crohn's disease. Gut. 1989 Jun;30(6):835–838. doi: 10.1136/gut.30.6.835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Mathison J. C., Virca G. D., Wolfson E., Tobias P. S., Glaser K., Ulevitch R. J. Adaptation to bacterial lipopolysaccharide controls lipopolysaccharide-induced tumor necrosis factor production in rabbit macrophages. J Clin Invest. 1990 Apr;85(4):1108–1118. doi: 10.1172/JCI114542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Maurelli A. T., Sansonetti P. J. Genetic determinants of Shigella pathogenicity. Annu Rev Microbiol. 1988;42:127–150. doi: 10.1146/annurev.mi.42.100188.001015. [DOI] [PubMed] [Google Scholar]
  11. Miura M., Zhu H., Rotello R., Hartwieg E. A., Yuan J. Induction of apoptosis in fibroblasts by IL-1 beta-converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3. Cell. 1993 Nov 19;75(4):653–660. doi: 10.1016/0092-8674(93)90486-a. [DOI] [PubMed] [Google Scholar]
  12. Munoz C., Carlet J., Fitting C., Misset B., Blériot J. P., Cavaillon J. M. Dysregulation of in vitro cytokine production by monocytes during sepsis. J Clin Invest. 1991 Nov;88(5):1747–1754. doi: 10.1172/JCI115493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Nett M. A., Cerretti D. P., Berson D. R., Seavitt J., Gilbert D. J., Jenkins N. A., Copeland N. G., Black R. A., Chaplin D. D. Molecular cloning of the murine IL-1 beta converting enzyme cDNA. J Immunol. 1992 Nov 15;149(10):3254–3259. [PubMed] [Google Scholar]
  14. Ranges G. E., Zlotnik A., Espevik T., Dinarello C. A., Cerami A., Palladino M. A., Jr Tumor necrosis factor alpha/cachectin is a growth factor for thymocytes. Synergistic interactions with other cytokines. J Exp Med. 1988 Apr 1;167(4):1472–1478. doi: 10.1084/jem.167.4.1472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Sarih M., Souvannavong V., Brown S. C., Adam A. Silica induces apoptosis in macrophages and the release of interleukin-1 alpha and interleukin-1 beta. J Leukoc Biol. 1993 Nov;54(5):407–413. doi: 10.1002/jlb.54.5.407. [DOI] [PubMed] [Google Scholar]
  16. Sartor R. B. Pathogenetic and clinical relevance of cytokines in inflammatory bowel disease. Immunol Res. 1991;10(3-4):465–471. doi: 10.1007/BF02919743. [DOI] [PubMed] [Google Scholar]
  17. Suda T., Hodgkin P., Lee F., Zlotnik A. Biological activity of recombinant murine interleukin-6 in interleukin-1 T cell assays. J Immunol Methods. 1989 Jun 21;120(2):173–178. doi: 10.1016/0022-1759(89)90239-1. [DOI] [PubMed] [Google Scholar]
  18. Wassef J. S., Keren D. F., Mailloux J. L. Role of M cells in initial antigen uptake and in ulcer formation in the rabbit intestinal loop model of shigellosis. Infect Immun. 1989 Mar;57(3):858–863. doi: 10.1128/iai.57.3.858-863.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Youngman K. R., Simon P. L., West G. A., Cominelli F., Rachmilewitz D., Klein J. S., Fiocchi C. Localization of intestinal interleukin 1 activity and protein and gene expression to lamina propria cells. Gastroenterology. 1993 Mar;104(3):749–758. doi: 10.1016/0016-5085(93)91010-f. [DOI] [PubMed] [Google Scholar]
  20. Zuckerman S. H., Evans G. F. Endotoxin tolerance: in vivo regulation of tumor necrosis factor and interleukin-1 synthesis is at the transcriptional level. Cell Immunol. 1992 Apr;140(2):513–519. doi: 10.1016/0008-8749(92)90216-c. [DOI] [PubMed] [Google Scholar]
  21. Zychlinsky A., Kenny B., Ménard R., Prévost M. C., Holland I. B., Sansonetti P. J. IpaB mediates macrophage apoptosis induced by Shigella flexneri. Mol Microbiol. 1994 Feb;11(4):619–627. doi: 10.1111/j.1365-2958.1994.tb00341.x. [DOI] [PubMed] [Google Scholar]
  22. Zychlinsky A., Prevost M. C., Sansonetti P. J. Shigella flexneri induces apoptosis in infected macrophages. Nature. 1992 Jul 9;358(6382):167–169. doi: 10.1038/358167a0. [DOI] [PubMed] [Google Scholar]
  23. Zychlinsky A. Programmed cell death in infectious diseases. Trends Microbiol. 1993 Jun;1(3):114–117. doi: 10.1016/0966-842x(93)90118-b. [DOI] [PubMed] [Google Scholar]

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