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Immunology. 2010 Jan;129(1):87-96. doi: 10.1111/j.1365-2567.2009.03152.x.

Inhibition of cyclooxygenase-2 impairs the expression of essential plasma cell transcription factors and human B-lymphocyte differentiation.

Author information

1
Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. matthew_bernard@urmc.rochester.edu

Abstract

Cyclooxygenase (Cox) inhibitors are among the most widely used and commonly prescribed medications. Relatively little is understood about their influence on human immune responses. Herein, we discovered a novel and important mechanism whereby non-steroidal anti-inflammatory drugs (NSAIDs) blunt human B-cell antibody production. We demonstrate that the Cox-2 selective small molecule inhibitors SC-58125 and NS-398 attenuate the production of human antibody isotypes including immunoglobulin M (IgM), IgG1, IgG2, IgG3 and IgG4. In addition, inhibition of Cox-2 significantly reduced the generation of CD38+ IgM+ and CD38+ IgG+ antibody-secreting cells. Interestingly, we discovered that inhibition of Cox-2 activity in normal human B cells severely reduced the messenger RNA and protein levels of the essential plasma cell transcription factor, Blimp-1. These observations were mirrored in Cox-2-deficient mice, which had reduced CD138+ plasma cells and a near loss of Blimp-1 expression. These new findings demonstrate a critical role for Cox-2 in the terminal differentiation of human B lymphocytes to antibody-secreting plasma cells. The use of NSAIDs may adversely influence the efficacy of vaccines, especially in the immunocompromised, elderly and when vaccines are weakly immunogenic.

PMID:
20050331
PMCID:
PMC2807489
DOI:
10.1111/j.1365-2567.2009.03152.x
[Indexed for MEDLINE]
Free PMC Article

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