Eicosanoid-Induced Store-Operated Calcium Entry in Dendritic Cells

Autor: Ping Shu, Mark L. Jordan, Hosea Huang, Beverly E. Barton, Kiyoshi Itagaki, Sean Taheri, Thomas F. Murphy
Rok vydání: 2011
Předmět:
Zdroj: Journal of Surgical Research. 169:301-310
ISSN: 0022-4804
DOI: 10.1016/j.jss.2009.10.016
Popis: Background Eicosanoids are generally recognized to exert potent immunomodulatory properties, including effects on T cell, antigen-presenting cell (APC), and dendritic cell (DC) maturation and function. Since DC maturation and function may also be regulated by store-operated calcium entry (SOCE), we hypothesized that the effects of eicosanoids on DC function may in part be regulated through changes in intracellular calcium. Methods DC derived from the bone marrow of male Balb/ByJ mice cultured for 7 d in the presence of granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) were used to study the effects of eicosanoids on SOCE and the resulting Ca 2+ mobilization. Results The 5-lipoxygenase (5-LO) products leukotriene B 4 (LTB 4 ) and LTD 4, but not LTC 4 , depleted Ca 2+ from DC endoplasmic reticulum stores. The specificity of LTB 4 and LTD 4 on Ca 2+ store-depletion was confirmed by the ability of the specific receptor antagonists, LY25583 and MK571, respectively, to abrogate Ca 2+ store depletion. RT-PCR demonstrated DC receptors for LTB 4 (BLT 1 and BLT 2 ) and the cysteinyl-LTs (CysLT 1 , CysLT 2 , and GPR17). We also detected transient receptor potential canonical (TRPC) 1, 2, 4, and 6 and stromal interaction molecule 1 (STIM1) on CD11c + DCs, suggesting these proteins also participate in DC SOCE. In contrast, the cyclooxygenase (CO) metabolite PGE 2 had no effect on DC Ca 2+ mobilization. Conclusions To our knowledge, these are the first observations of distinct effects of eicosanoids on DC Ca 2+ mobilization, which may have important implications for the regulation of DC maturation at sites of immune and non-immune inflammation.
Databáze: OpenAIRE
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