Cyclooxygenase-1 Orchestrates Germinal Center Formation and Antibody Class-Switch via Regulation of IL-17

被引:32
作者
Blaho, Victoria A. [1 ]
Buczynski, Matthew W. [3 ]
Dennis, Edward A. [3 ,4 ]
Brown, Charles R. [1 ,2 ]
机构
[1] Univ Missouri, Dept Vet Pathobiol, Columbia, MO 65211 USA
[2] Univ Missouri, Dept Mol Microbiol & Immunol, Columbia, MO 65211 USA
[3] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA
[4] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA
基金
美国国家卫生研究院;
关键词
EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; BORRELIA-BURGDORFERI; LYME-DISEASE; T-CELLS; INTERLEUKIN-6-DEFICIENT MICE; B-LYMPHOCYTES; CYCLIC-AMP; ARTHRITIS; ACTIVATION;
D O I
10.4049/jimmunol.0901499
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The cyclooxygenase (COX) enzymes are known modulators of innate immune cell function; however, their contributions to adaptive immunity are relatively unknown. We investigated the roles of COX-1 and COX-2 in the humoral immune response to infection with the Lyme disease pathogen Borrelia burgdorferi. We report that in vitro, murine B cells constitutively expressed COX-1 and up-regulated expression of both COX-1 and COX-2 as well as their products PGE(2), PGF(2 alpha), and thromboxane B-2 and their receptors following stimulation with B. burgdorferi or anti-CD40. In vitro inhibition of COX-1 and/or COX-2 in murine IS cells resulted in decreased eicosanoid production and altered Ab production. Importantly, infection of mice lacking COX-1, but not COX-2, activity resulted in a defect in Ig class-switching and a lack of Borrelia-specific IgG production. This defect correlated with decreased germinal center formation and IL-6 and IL-17 production, and it could be partially recovered by restoration of IL-6, but fully recovered by IL-17. Furthermore, sera from COX-1 inhibitor-treated mice were dramatically less effective in killing B. burgdorferi, but borreliacidal activity was restored in COX-1 inhibitor-treated mice administered IL-17. We conclude that IL-17 plays a role in Ab production and Ig class-switching in response to infection and that COX-1 is a critical, previously unrecognized regulator of this response. The Journal of Immunology, 2009, 183: 5644-5653.
引用
收藏
页码:5644 / 5653
页数:10
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