Compensatory prostaglandin E2 biosynthesis in cyclooxygenase 1 or 2 null cells

Kanyawim Kirtikara, Scott G. Morham, Rajendra Raghow, Stanley J.F. Laulederkind, Takuro Kanekura, Sarita Goorha, Leslie R. Ballou

Research output: Contribution to journalArticle

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Abstract

Prostaglandin E2 (PGE2) production in immortalized, nontransformed cells derived from wild-type, cyclooxygenase 1-deficient (COX-1(-/-)) or cyclooxygenase 2-deficient (COX-2(-/-)) mice was examined after treatment with interleukin (IL)-1β, tumor necrosis factor or, acidic fibroblast growth factor, and phorbol ester (phorbol myristate acetate). Compared with their wild-type counterparts, COX-1(-/-) or COX-2(-/-) cells exhibited substantially enhanced expression of the remaining functional COX gene. Furthermore, both basal and IL-1-induced expression of cytosolic phospholipase A2 (cPLA2), a key enzyme-regulating substrate mobilization for PGE2 biosynthesis, was also more pronounced in both COX-1(-/-) and COX- 2(-/-) cells. Thus, COX-1(-/-) and COX-2(-/-) cells have the ability to coordinate the upregulation of the alternate COX isozyme as well as cPLA2 genes to overcome defects in prostaglandin biosynthetic machinery. The potential for cells to alter and thereby compensate for defects in the expression of specific genes such as COX has significant clinical implications given the central role of COX in a variety of disease processes and the widespread use of COX inhibitors as therapeutic agents.

Original languageEnglish (US)
Pages (from-to)517-523
Number of pages7
JournalJournal of Experimental Medicine
Volume187
Issue number4
DOIs
StatePublished - Feb 16 1998

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Null Lymphocytes
Cyclooxygenase 1
Cyclooxygenase 2
Dinoprostone
Cytosolic Phospholipases A2
Interleukin-1
Fibroblast Growth Factor 1
Phorbol Esters
Tetradecanoylphorbol Acetate
Isoenzymes
Genes
Prostaglandins
Up-Regulation
Tumor Necrosis Factor-alpha
Gene Expression
Enzymes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Kirtikara, K., Morham, S. G., Raghow, R., Laulederkind, S. J. F., Kanekura, T., Goorha, S., & Ballou, L. R. (1998). Compensatory prostaglandin E2 biosynthesis in cyclooxygenase 1 or 2 null cells. Journal of Experimental Medicine, 187(4), 517-523. https://doi.org/10.1084/jem.187.4.517

Compensatory prostaglandin E2 biosynthesis in cyclooxygenase 1 or 2 null cells. / Kirtikara, Kanyawim; Morham, Scott G.; Raghow, Rajendra; Laulederkind, Stanley J.F.; Kanekura, Takuro; Goorha, Sarita; Ballou, Leslie R.

In: Journal of Experimental Medicine, Vol. 187, No. 4, 16.02.1998, p. 517-523.

Research output: Contribution to journalArticle

Kirtikara, K, Morham, SG, Raghow, R, Laulederkind, SJF, Kanekura, T, Goorha, S & Ballou, LR 1998, 'Compensatory prostaglandin E2 biosynthesis in cyclooxygenase 1 or 2 null cells', Journal of Experimental Medicine, vol. 187, no. 4, pp. 517-523. https://doi.org/10.1084/jem.187.4.517
Kirtikara, Kanyawim ; Morham, Scott G. ; Raghow, Rajendra ; Laulederkind, Stanley J.F. ; Kanekura, Takuro ; Goorha, Sarita ; Ballou, Leslie R. / Compensatory prostaglandin E2 biosynthesis in cyclooxygenase 1 or 2 null cells. In: Journal of Experimental Medicine. 1998 ; Vol. 187, No. 4. pp. 517-523.
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