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Proinflammatory actions of thromboxane receptors to enhance cellular immune responses.

Publication ,  Journal Article
Thomas, DW; Rocha, PN; Nataraj, C; Robinson, LA; Spurney, RF; Koller, BH; Coffman, TM
Published in: J Immunol
December 15, 2003

Metabolism of arachidonic acid by the cyclo-oxygenase (COX) pathway generates a family of prostanoid mediators. Nonsteroidal anti-inflammatory drugs (NSAIDs) act by inhibiting COX, thereby reducing prostanoid synthesis. The efficacy of these agents in reducing inflammation suggests a dominant proinflammatory role for the COX pathway. However, the actions of COX metabolites are complex, and certain prostanoids, such as PGE(2), in some circumstances actually inhibit immune and inflammatory responses. In these studies, we examine the hypothesis that anti-inflammatory actions of NSAIDs may be due, in part, to inhibition of thromboxane A(2) synthesis. To study the immunoregulatory actions of thromboxane A(2), we used mice with a targeted disruption of the gene encoding the thromboxane-prostanoid (TP) receptor. Both mitogen-induced responses and cellular responses to alloantigen were substantially reduced in TP(-/-) spleen cells. Similar attenuation was observed with pharmacological inhibition of TP signaling in wild-type splenocytes, suggesting that reduced responsiveness was not due to subtle developmental abnormalities in the TP-deficient mice. The absence of TP receptors reduced immune-mediated tissue injury following cardiac transplant rejection, an in vivo model of intense inflammation. Taken together, these findings show that thromboxane augments cellular immune responses and inflammatory tissue injury. Specific inhibition of the TP receptor may provide a more precise approach to limit inflammation without some of the untoward effects associated with NSAIDs.

Duke Scholars

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

December 15, 2003

Volume

171

Issue

12

Start / End Page

6389 / 6395

Location

United States

Related Subject Headings

  • Thromboxane-A Synthase
  • T-Lymphocytes
  • Spleen
  • Ribonucleases
  • Receptors, Thromboxane
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Lymphocyte Culture Test, Mixed
 

Citation

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Thomas, D. W., Rocha, P. N., Nataraj, C., Robinson, L. A., Spurney, R. F., Koller, B. H., & Coffman, T. M. (2003). Proinflammatory actions of thromboxane receptors to enhance cellular immune responses. J Immunol, 171(12), 6389–6395. https://doi.org/10.4049/jimmunol.171.12.6389
Thomas, Dennis W., Paulo N. Rocha, Chandra Nataraj, Lisa A. Robinson, Robert F. Spurney, Beverly H. Koller, and Thomas M. Coffman. “Proinflammatory actions of thromboxane receptors to enhance cellular immune responses.J Immunol 171, no. 12 (December 15, 2003): 6389–95. https://doi.org/10.4049/jimmunol.171.12.6389.
Thomas DW, Rocha PN, Nataraj C, Robinson LA, Spurney RF, Koller BH, et al. Proinflammatory actions of thromboxane receptors to enhance cellular immune responses. J Immunol. 2003 Dec 15;171(12):6389–95.
Thomas, Dennis W., et al. “Proinflammatory actions of thromboxane receptors to enhance cellular immune responses.J Immunol, vol. 171, no. 12, Dec. 2003, pp. 6389–95. Pubmed, doi:10.4049/jimmunol.171.12.6389.
Thomas DW, Rocha PN, Nataraj C, Robinson LA, Spurney RF, Koller BH, Coffman TM. Proinflammatory actions of thromboxane receptors to enhance cellular immune responses. J Immunol. 2003 Dec 15;171(12):6389–6395.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

December 15, 2003

Volume

171

Issue

12

Start / End Page

6389 / 6395

Location

United States

Related Subject Headings

  • Thromboxane-A Synthase
  • T-Lymphocytes
  • Spleen
  • Ribonucleases
  • Receptors, Thromboxane
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Lymphocyte Culture Test, Mixed