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. Published by Elsevier Inc.
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. Published by Elsevier Inc.
Authors: Jens Dannull; Tristan Schneider; Walter T Lee; Nicole de Rosa; Douglas S Tyler; Scott K Pruitt Journal: Blood Date: 2012-02-08 Impact factor: 22.113