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Acta Physiologica Congress

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Acta Physiologica 2013; Volume 207, Supplement 694
92nd Annual Meeting of the German Physiological Society
3/2/2013-3/5/2013
Heidelberg, Germany


ALTERED REGULATION OF CYTOSOLIC CA2+ CONCENTRATION IN DENDRITIC CELLS FROM KLOTHO HYPOMORPHIC MICE
Abstract number: P041

Nurbaeva 1   *M. , Shumilina 1  E., Yang 1  W., Schmid 1  E., Leibrock 1  C., Lang 1  F.

1 University of Tuebingen, Department of Physiology, Tuebingen, Germany

Background:

Function of dendritic cells (DCs), antigen-presenting cells regulating naïve T-cells, is regulated by cytosolic Ca2+ concentration ([Ca2+]i). [Ca2+]i is increased by store operated Ca2+ entry and decreased by K+-independent (NCX) and K+-dependent (NCKX) Na+/Ca2+ exchangers. NCKX exchangers are stimulated by immunosuppressive 1,25(OH)2D3. Formation of 1,25(OH)2D3 is inhibited by anti-aging protein klotho. Thus, 1,25(OH)2D3 plasma levels are excessive in klotho-deficient mice ( klothohm ). The present study explored whether klotho-deficiency modifies [Ca2+]i regulation in DCs.

Methods/Results:

DCs were isolated from bone marrow of klothohm mice and corresponding wild type mice ( klotho+/+ ) and cultured for 7-9 days with GM-CSF. According to MHCII and CD86 expression, differentiation and lipopolysaccharide (LPS)-induced maturation was similar in klothohm and klotho+/+ DCs. However, NCKX activity was significantly enhanced in klothohm DCs. The [Ca2+]i increase upon acute application of LPS (1 µg/ml) was significantly lower in klothohm DCs than in klotho+/+ DCs, a difference reversed by NCKX-blocker 3’,4’-dichlorobenzamyl (DBZ, 10 µM). CCL21-dependent migration was significantly less in klothohm DCs than in klotho+/+ DCs. NCKX activity could be enhanced by pretreatment of klotho+/+ DC precursors with 1,25(OH)2D3 the first 2 days after isolation from bone marrow. Feeding klothohm mice a vitamin D deficient diet decreased NKCX activity, augmented LPS-induced increase of [Ca2+]i, and enhanced migration of klothohm DCs, thus dissipating the differences between klothohm DCs and klotho+/+ DCs.

Conclusions:

Klotho deficiency up-regulates Na+/Ca2+ exchange activity and thus blunts the increase of [Ca2+]i following LPS exposure and CCL21-mediated migration. The effects are in large part due to excessive 1,25(OH)2D3 formation.

To cite this abstract, please use the following information:
Acta Physiologica 2013; Volume 207, Supplement 694 :P041

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