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Concordant Modulation of Cysteinyl Leukotriene Receptor Expression by IL-4 and IFN- on Peripheral Immune Cells

Asthma and Allergic Disease Center, Beirne Carter Center for Immunology Research, Departments of Medicine, University of Virginia Health System, Charlottesville, Virginia

Correspondence and requests for reprints should be addressed to John W. Steinke, Asthma and Allergic Disease Center, Box 801355, University of Virginia Health System, Charlottesville, VA 22908. E-mail: js3ch{at}virginia.edu

Arachidonic acid can be metabolized to form a group of compounds known as the cysteinyl leukotrienes (CysLT) that bind to one of two receptors to mediate their actions. On circulating cells, expression of the leukotriene receptors is low, but in inflamed tissue the receptor number is dramatically increased. We hypothesized that the cytokine milieu present during inflammation can increase receptor expression on infiltrating immune cells. Various cell populations were purified from peripheral blood and stimulated in vitro with cytokines characteristic of allergic inflammatory disorders, and CysLT receptor expression was measured using quantitative PCR analysis, Western blot, and flow cytometry. IL-4, but not IL-13, was able to significantly induce mRNA and protein levels for both CysLT receptor 1 and 2 from T cells and B cells. CysLT2 receptor expression was also significantly increased in monocytes and eosinophils after IL-4 stimulation. Surprisingly, CysLT2 receptor expression was increased in monocytes, T cells, and B cells when IFN- was used as the stimulus. Factors involved in eosinophil growth and survival were tested for their ability to alter CysLT receptor expression. These results support the concept that cytokines increase expression of both receptors on lymphocytes and granulocytes, allowing these cells to be more responsive to secreted leukotrienes at sites of inflammation.

Key Words: cysteinyl leukotriene receptor • T cell • B cell • eosinophil • cytokine

CLINICAL RELEVANCE These results show that the inflammatory milieu in asthma can increase both type 1 and 2 cysteinyl leukotriene receptor expression. Increased receptor expression will make these cells more responsive to leukotriene expression and increase the severity of disease.