Additional file 2: of The influence of calcitonin gene-related peptide on markers of bone metabolism in MG-63 osteoblast-like cells co-cultured with THP-1 macrophage-like cells under virtually osteolytic conditions

Data and statistical analysis of particle- or LPS-activated THP-1/MG-63 co-cultures treated with the neuropeptide CGRP. (XLSX 19 kb

Additional file 2: Figure S2. of Human mesenchymal stromal/stem cells acquire immunostimulatory capacity upon cross-talk with natural killer cells and might improve the NK cell function of immunocompromised patients

CD56dim NK cells do not respond to CCR2 ligands. NK cells were incubated in the absence (–) or presence of 0.5 ng/ml of recombinant human CCL2, CCL8, CCL7, and CCL12, or with conditioned medium (CM) from MSCs for 12 h. Thereafter, the cells were stimulated with IL-12 (1 ng/ml) and IL-18 (5 ng/ml). Dot plots of intracellular staining of IFN-γ in gated CD3–CD56dim NK cells (gating strategy as shown in Fig. 1d). Data are representative for one out of five experiments. The threshold of positive staining for IFN-γ was set according to the isotype control (iso). Numbers indicate the percentage of IFN-γ-positive NK cells. MSC mesenchymal stromal/stem cell, CCL C-C ligand, IFN interferon. (PDF 36 kb

Inhibition of Na(+)/H(+)-exchanger with sabiporide attenuates the downregulation and uncoupling of the myocardial β-adrenoceptor system in failing rabbit hearts

1. Chronic heart failure (HF) is characterized by left ventricular (LV) structural remodeling, impaired function, increased circulating noradrenaline (NA) levels and impaired responsiveness of the myocardial β-adrenoceptor (βAR)-adenylyl cyclase (AC) system. In failing hearts, inhibition of the sodium/proton-exchanger (NHE)-1 attenuates LV remodeling and improves LV function. The mechanism(s) involved in these cardioprotective effects remain(s) unclear, but might involve effects on the impaired βAR-AC system. 2. Therefore, we investigated whether NHE-1 inhibition with sabiporide (SABI; 30 mg kg(−1) day(−1) p.o.) might affect myocardial βAR density and AC activity in relation to changes in LV end-diastolic diameter (LVEDD) and LV systolic fractional shortening (LVS-FS) after 3 weeks of rapid LV pacing in rabbits. 3. After 3 weeks of rapid LV pacing LVEDD was significantly increased (Shams 17±0.2 mm, n=9 vs 3wksHF 20±0.5 mm, n=8; P<0.05) and LVS-FS decreased (Shams 31±1%, n=9 vs 3wksHF 10±1%, n=8; P<0.05). SABI treatment significantly improved LV function independent of whether rabbits were treated after 1 week of pacing (3wksHF+2wksSABI (n=7): LVEDD 18±1 mm; LVS-FS 16±4%) or before pacing (3wksHF+3wksSABI (n=9): LVEDD 18±1 mm; LVS-FS 18±6%). After 3 weeks of rapid LV pacing, SABI treatment significantly attenuated increases in serum NA content (Shams 0.83±0.19, 3wksHF 2.68±0.38, 3wksHF+2wksSABI 1.22±0.32, 3wksHF+3wksSABI 1.38±0.33 ng ml(−1)). Moreover, βAR density (Shams 64±5, 3wksHF 38±3, 3wksHF+2wksSABI 48±4, 3wksHF+3wksSABI 55±3 fmol mg(−1) protein) and responsiveness (isoprenaline-stimulated AC activity. (Shams 57.6±4.9, 3wksHF 36.3±6.0, 3wksHF+2wksSABI 56.9±6.0, 3wksHF+3wksSABI 54.5±4.8 pmol cyclic AMP mg(−1) protein(−1) min(−1)) were significantly improved in SABI-treated rabbits. 4. From the present data we cannot address whether the improved βAR-AC system permitted improved LV function and/or whether the improved LV function resulted in less activation of the sympathetic nervous system and by this in a reduced stimulation of the βAR-AC system. Accordingly, additional studies are needed to fully establish the cause-and-effect relationship between NHE-1 inhibition and the restoration of the myocardial βAR system