Abstract
We investigated whether an interleukin 1 receptor antagonist (IL-1ra) altered cellular release of prostanoids and leukotrienes in a transformed colonic cell line (CACO-2) in the presence of proinflammatory stimuli. Cellular inflammation was induced by treatment with lipopolysaccharide (LPS) or the cytokine, interleukin 1 beta (IL-1β). In a separate set of experiments, cells were pretreated with IL-1ra prior to exposure to LPS or IL-1β. Prostaglandin E2 and leukotriene B4 (LTB4) levels were quantified by ELISA assays. Both LPS and IL-1β exposure were noted to stimulate cellular PGE2 release, a response which was significantly inhibited by IL-1ra treatment. Either stimulant when administered alone failed to stimulate release of LTB4. When administered after IL-1ra pretreatment however, both stimuli caused a significant increase in LTB4 release. These results suggest that a cytokine receptor antagonist can selectively influence eicosanoid production in this cell line. Furthermore, this study suggests that a IL-1ra may have a future clinical role in the treatment of inflammatory disorders of the colon which are intimately linked to enhanced eicosanoid synthesis.
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- Aspinall R. L., Cammarata P. S. Effect of prostaglandin E2 on adjuvant arthritis. Nature. 1969 Dec 27;224(5226):1320–1321. doi: 10.1038/2241320a0. [DOI] [PubMed] [Google Scholar]
- Campbell C. A., Walker-Smith J. A., Hindocha P., Adinolfi M. Acute phase proteins in chronic inflammatory bowel disease in childhood. J Pediatr Gastroenterol Nutr. 1982;1(2):193–200. doi: 10.1097/00005176-198201020-00007. [DOI] [PubMed] [Google Scholar]
- Chambers R. E., Stross P., Barry R. E., Whicher J. T. Serum amyloid A protein compared with C-reactive protein, alpha 1-antichymotrypsin and alpha 1-acid glycoprotein as a monitor of inflammatory bowel disease. Eur J Clin Invest. 1987 Oct;17(5):460–467. doi: 10.1111/j.1365-2362.1987.tb01143.x. [DOI] [PubMed] [Google Scholar]
- Cybulsky M. I., Chan M. K., Movat H. Z. Acute inflammation and microthrombosis induced by endotoxin, interleukin-1, and tumor necrosis factor and their implication in gram-negative infection. Lab Invest. 1988 Apr;58(4):365–378. [PubMed] [Google Scholar]
- Durum S. K., Schmidt J. A., Oppenheim J. J. Interleukin 1: an immunological perspective. Annu Rev Immunol. 1985;3:263–287. doi: 10.1146/annurev.iy.03.040185.001403. [DOI] [PubMed] [Google Scholar]
- Elner V. M., Strieter R. M., Elner S. G., Baggiolini M., Lindley I., Kunkel S. L. Neutrophil chemotactic factor (IL-8) gene expression by cytokine-treated retinal pigment epithelial cells. Am J Pathol. 1990 Apr;136(4):745–750. [PMC free article] [PubMed] [Google Scholar]
- Ham E. A., Soderman D. D., Zanetti M. E., Dougherty H. W., McCauley E., Kuehl F. A., Jr Inhibition by prostaglandins of leukotriene B4 release from activated neutrophils. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4349–4353. doi: 10.1073/pnas.80.14.4349. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hannum C. H., Wilcox C. J., Arend W. P., Joslin F. G., Dripps D. J., Heimdal P. L., Armes L. G., Sommer A., Eisenberg S. P., Thompson R. C. Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor. Nature. 1990 Jan 25;343(6256):336–340. doi: 10.1038/343336a0. [DOI] [PubMed] [Google Scholar]
- Kaminski D. L., Feinstein W. K., Deshpande Y. G. The production of experimental cholecystitis by endotoxin. Prostaglandins. 1994 Mar;47(3):233–245. doi: 10.1016/0090-6980(94)90063-9. [DOI] [PubMed] [Google Scholar]
- Prantera C., Davoli M., Lorenzetti R., Pallone F., Marcheggiano A., Iannoni C., Mariotti S. Clinical and laboratory indicators of extent of ulcerative colitis. Serum C-reactive protein helps the most. J Clin Gastroenterol. 1988 Feb;10(1):41–45. doi: 10.1097/00004836-198802000-00010. [DOI] [PubMed] [Google Scholar]
- Rachmilewitz D., Simon P. L., Schwartz L. W., Griswold D. E., Fondacaro J. D., Wasserman M. A. Inflammatory mediators of experimental colitis in rats. Gastroenterology. 1989 Aug;97(2):326–337. doi: 10.1016/0016-5085(89)90068-1. [DOI] [PubMed] [Google Scholar]
- Satsangi J., Wolstencroft R. A., Cason J., Ainley C. C., Dumonde D. C., Thompson R. P. Interleukin 1 in Crohn's disease. Clin Exp Immunol. 1987 Mar;67(3):594–605. [PMC free article] [PubMed] [Google Scholar]
- Sirko S., Bishai I., Coceani F. Prostaglandin formation in the hypothalamus in vivo: effect of pyrogens. Am J Physiol. 1989 Mar;256(3 Pt 2):R616–R624. doi: 10.1152/ajpregu.1989.256.3.R616. [DOI] [PubMed] [Google Scholar]
- Stratton M. D., Chandel B., Deshpande Y., Kaminski D. L., Li A. P., Vernava A. M., Longo W. E. The effect of Clostridium difficile toxin on colonocyte prostanoid activity. Prostaglandins. 1994 Dec;48(6):367–375. doi: 10.1016/0090-6980(94)90003-5. [DOI] [PubMed] [Google Scholar]
- Ulich T. R., Busser K., Longmuir K. J. Cytokine- and calcium ionophore A23187-mediated arachidonic acid metabolism in neutrophils. Cytokine. 1990 Jul;2(4):280–286. doi: 10.1016/1043-4666(90)90029-s. [DOI] [PubMed] [Google Scholar]
- Ulich T. R., del Castillo J., Keys M., Granger G. A., Ni R. X. Kinetics and mechanisms of recombinant human interleukin 1 and tumor necrosis factor-alpha-induced changes in circulating numbers of neutrophils and lymphocytes. J Immunol. 1987 Nov 15;139(10):3406–3415. [PubMed] [Google Scholar]
- Wiechelman K. J., Braun R. D., Fitzpatrick J. D. Investigation of the bicinchoninic acid protein assay: identification of the groups responsible for color formation. Anal Biochem. 1988 Nov 15;175(1):231–237. doi: 10.1016/0003-2697(88)90383-1. [DOI] [PubMed] [Google Scholar]
- Zurier R. B., Hoffstein S., Weissmann G. Suppression of acute and chronic inflammation in adrenalectomized rats by pharmacologic amounts of prostaglandins. Arthritis Rheum. 1973 Sep-Oct;16(5):606–618. doi: 10.1002/art.1780160505. [DOI] [PubMed] [Google Scholar]
- Zurier R. B., Quagliata F. Effect of prostaglandin E 1 on adjuvant arthritis. Nature. 1971 Dec 3;234(5327):304–305. doi: 10.1038/234304a0. [DOI] [PubMed] [Google Scholar]