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Comparative evaluation of arachidonic acid (AA)- and tetradecanoylphorbol acetate (TPA)-induced dermal inflammation

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Abstract

The effects of topical application of arachidonic acid (AA) or phorbol ester, tetradecanoylphorbol 13-acetate (TPA), on edema response, vascular permeability, MPO, NAG, and generation of eicosanoids were studied in two murine models of cutaneous inflammation. AA produced a short-lived edema response with a rapid onset that was associated with marked increases in levels of prostaglandins (PGE2, 6-keto-PGF1α, PGF2α), thromboxane B2 (TxB2) and leukotriene B4 (LTB4), with smaller increases in levels of LTC4. TPA produced a longer-lasting edema that was associated with marked influx of neutrophils and predominant formation of LTB4 along with significant changes in levels of TxB2. Circulating T lymphocytes have no apparent role in the acute inflammatory responses induced by either agent. Arachidonic acid-induced vascular permeability preceded the edema response and neutrophil influx, whereas TPA-induced vascular permeability paralleled the edema response and influx of neutrophils. Mast cells appear to be important in the complete expression of inflammatory response, i.e., edema, cellular influx, and vascular permeability induced by either AA or TPA, as these responses were blunted in mast cell-deficient mice. Inhibitors of CO or 5-LO attenuated inflammatory responses in both models. The LTB4 receptor antagonist, SC-41930, inhibited the inflammatory response to TPA but had little effect on that initiated by AA. This suggests that LTB4 is an important mediator in the phorbol ester-induced inflammatory response, whereas peptidoleukotrienes and prostaglandins regulate vascular permeability responses in the arachidonate model.

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References

  1. Wershill, B. K., Y. A. Mekori, T. Murakami, andS. J. Galli. 1987.125I-Fibrin deposition in IgE-dependent immediate hypersensitivity reactions in mouse skin. Demonstration of the role of mast cells using genetically mast cell-deficient mice locally reconstituted with cultured mast cells.J. Immunol. 139:2605–2614.

    Google Scholar 

  2. Yano, H., B. K. Wershill, N. Arizono, andS. J. Galli. 1989. Substance-P induced augmentation of cutaneous vascular permeability in mice is mast cell dependent.J. Clin. Invest. 84:1276–1296.

    Google Scholar 

  3. Ramos, B. F., Y. Zhang, R. Qureshi, andB. A. Jakschik. 1991. Mast cells are critical for production of leukotrienes responsible for neutrophil recruitment in immune complex-induced peritonitis in mice.J. Immunol. 147:1636–1641.

    Google Scholar 

  4. Ramos, B. F., R. Qureshi, K. M. Olsen, andB. A. Jakschik. 1990. The importance of mast cells for the neutrophil influx in immune complex-induced peritonitis in mice.J. Immunol. 145:1866–1873.

    Google Scholar 

  5. Ramos, B. F., Y. Zhang, V. Angkachatchai, andB. A. Jakschik. 1992. Mast cells regulate vascular permeability changes in Arthus reaction.J. Pharmacol. Exp. Ther. 262:559–565.

    Google Scholar 

  6. Zhang, Y., B. F. Ramos, andB. A. Jakschik. 1991. Augmentation of reverse Arthus reaction by mast cells in mice.J. Clin. Invest. 88:841–846.

    Google Scholar 

  7. Zhang, Y., B. F. Ramos, andB. A. Jakschik. 1992. Neutrophil recruitment by tumor necrosis factor from mast cells in immune complex peritonitis.Science 258:1957–1959.

    Google Scholar 

  8. Chang, J., R. P. Carlson, L. O'Neill-Davis, B. Lamb, R. N. Sharma, andA. J. Lewis. 1986. Correlation between mouse skin inflammation induced by arachidonic acid and eicosanoid synthesis.Inflammation 10:205–214.

    Google Scholar 

  9. Opas, E. E., R. J. Bonney, andJ. L. Humes. 1985. Prostaglandin and leukotriene synthesis in mouse ears inflamed by arachidonic acid.J. Invest. Dermatol. 84:253–256.

    Google Scholar 

  10. Davies, P., P. J. Bailey, R. Goldberg, andW. A. Ford-Hutchinson. 1984. The role of arachidonic acid oxygenation products in pain and inflammation.Annu. Rev. Immunol. 2:337–357.

    Google Scholar 

  11. Williams, T. J. 1979. Prostaglandin E2, prostaglandin I2 and the vascular changes in inflammation.Br. J. Pharmacol. 65:517–524.

    Google Scholar 

  12. Williams, T. J. 1983. Interactions between prostaglandins leukotrienes and other mediators of inflammation.Br. Med. Bull. 30:239–242.

    Google Scholar 

  13. Humes, J. L., E. E. Opas, andR. J. Bonney. 1989. Arachidonic acid metabolites in mouse ear edema.In Advances in Inflammation Research, Vol. 11. I. Otterness, A. L. Lewis, and R. Capetola, editors. Raven Press, New York. 57–65.

    Google Scholar 

  14. Carlson, R. P., L. O'Neill-Davis, J. Chang, andA. J. Lewis. 1985. Modulation of mouse ear edema by cyclooxygenase and lipoxygenase inhibitors and other pharmacologic agents.Agents Actions 17:197–204.

    Google Scholar 

  15. Young, J. M., J. A. Spires, C. D. Bedford, B. Wagner, S. J. Ballron, andL. M. De Young. 1984. The mouse ear inflammatory response to topical arachidonic acid.J. Invest. Dermatol. 82:367–371.

    Google Scholar 

  16. Carter, G. W., P. R. Young, D. H. Albert, J. Bouska, R. Dyer, R. L. Bell, J. B. Summers, andD. W. Brooks. 1991. 5-Lipoxygense inhibitory activity of zileuton.J. Pharmacol. Exp. Ther. 256:929–937.

    Google Scholar 

  17. Ashendel, C. L., andR. K. Boutwell. 1979. Prostaglandin E and F levels in mouse dermis are increased by tumor promoting phorbol esters.Biochem. Biophys. Res. Commun. 90:623–627.

    Google Scholar 

  18. Marks, F., G. Fusterberger, andE. Kowantzki. 1981. Prostaglandin E-mediated mitogenic stimulation of mouse epidermis in vivo by divalent cation ionophore A 23187 and by tumor promotor 12-O-tetradecanoylphorbol-13-acetate.Cancer Res. 41:696–702.

    Google Scholar 

  19. Fustenberger, G., andF. Marks. 1982. Early prostaglandin E synthesis is an obligatory event in induction of cell proliferation in mouse epidermis in vivo by phorbol ester TPA.Biochem. Biophys. Res. Commun. 92:749–756.

    Google Scholar 

  20. Young, J. M., B. M. Wagner, andD. A. Spires. 1983. Tachyphylaxis in 12-O-tetradecanoylphorbol-13-acetate and arachidonic acid-induced ear edema.J. Invest. Dermatol. 80:48–52.

    Google Scholar 

  21. Ackerman, N. R., E. C. Arner, H. Galbraith, R. R. Harris, B. D. Jaffe, andW. M. Macki. 1986. Anti-inflammatory consequences of 5-lipoxygenase inhibition.Adv. Prostaglandin, Thromboxane, Leukotriene Res. 16:47–56.

    Google Scholar 

  22. Gillard, J., A. W. Ford-Hutchinson, C. Chan, S. Charleson, D. Denis, R. Foster, R. Frtlin, S. Leger, C. S. McFarlane, H. Morton, H. Piechuta, D. Riendeau, C. A. Rouzer, J. Rokash, R. Young, D. E. McIntyre, L. Peterson, G. Bach, E. Eiermann, S. Hopple, J. Humes, L. Hupe, S. Luell, J. Metzger, R. Mauer, D. K. Miller, E. Opas, andS. Pacholok. 1989. L-663,356 (MK-886) {3-[l-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2-dimethylpropanoic acid}, a novel, orally active leukotriene biosynthesis inhibitor.Can. J. Physiol. Pharmacol. 67:456–464.

    Google Scholar 

  23. Fretand, D., S. Widomski, B. Tsai, J. Zemaitis, S. Levin, S. Djuric, R. Shone, andT. Gaginella. 1990. Effect of the LTB4 receptor antagonist, SC-41930 on colonic inflammation in rat, guinea pig and rabbit.J. Pharmacol. Exp. Ther. 255:572–576.

    Google Scholar 

  24. Fretland, D., D. Widomski, J. Zemaitis, S. Djuric, andR. Shone. 1990. Effect of a leukotriene receptor antagonist on LTB4 -induced neutrophil chemotaxis in cavine dermis.Inflammation 13:601–605.

    Google Scholar 

  25. Villani-Price, D., D. Yang, R. Walsh, D. Fretland, R. Keith, G. Kokan, T. Gaginella, andB. S. Tsai. 1992. Multiple actions of the leukotriene B4 receptor antagonist, SC-41930.J. Pharmacol. Exp. Ther. 260:187–191.

    Google Scholar 

  26. Fleisch, J. H., L. E. Rinkema, K. D. Haisch, T. Swanson-Bean, T. Goodson, P. P. K. Ho, andW. S. Marshall. 1985. LY-171883 {l-[2-hydroxy-3-propyl-4-(1H-tetrazol-5-yl)butoxy-phenylethanone]}, an orally active leukotriene D4 antagonist.J. Pharmacol. Exp. Ther. 233:148–157.

    Google Scholar 

  27. Bradley, P. B., D. A. Pribat, R. O. Christensen, andG. Rothstein. 1982. Measurement of cutaneous inflammation: Estimation of neutrophil content with an enzyme marker.J. Invest. Dermatol. 78:206–209.

    Google Scholar 

  28. Schultz, J., andK. Kaminker. 1962, Myeloperoxidase of the leucocyte of normal human blood I. Content and localization.Arch. Biochem. Biophys. 525:37–44.

    Google Scholar 

  29. Bailey, P., J. A. Sturm, andB. Lopez-Ramos. 1982. A biochemical study of the cotton pellet granuloma in the rat.Biochem. Pharmacol. 31:1213–1218.

    Google Scholar 

  30. Griswold, D. E., S. Hoffstein, P. J. Marshall, D. F. Webb, L. Hillegass, P. E. Bender, andN. Hanna. 1983. Inhibition of inflammatory cell infiltration by bicyclic imidazoles, SK&F 86002 and SK&F 104493.Inflammation 13:727–739.

    Google Scholar 

  31. Otterness, I. G., andM. L. Blivan. 1985. Laboratory models for testing non-steroidal antiinflammatory drugs.In Nonsteroidal Antiinflammatory Drugs. J. G. Lobardino, editor. John Wiley, New York. 116–252.

    Google Scholar 

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Authors and Affiliations

  1. Inflammatory Diseases Research Searle Research & Development, c/o Monsanto Company, 63198, St. Louis, Missouri

    Tadimeti S. Rao, Jerry L. Currie, Alexander F. Shaffer & Peter C. Isakson

  2. The Salk Institute of Biotechnology/Industrial Assoc., Inc. (SIBIA), 505 Coast Blvd., 92307-4641, South La Jolla, CA

    Tadimeti S. Rao

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  1. Tadimeti S. Rao
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Rao, T.S., Currie, J.L., Shaffer, A.F. et al. Comparative evaluation of arachidonic acid (AA)- and tetradecanoylphorbol acetate (TPA)-induced dermal inflammation. Inflammation 17, 723–741 (1993). https://doi.org/10.1007/BF00920477

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