Role of glucocorticoid on interleukin-6-induced cellular functions in the mouse macrophage cell line (Mm 1)

AbstractTo discover a role of glucocorticoid on interleukin-6 (IL-6)-induced responses of a macrophage, we investigated the effect of IL-6 and/or dexamethasone (Dex) on cellular functions of a mouse macrophage cell line (Mm1 cells). The results obtained were as follows. (1) Dex decreased the accumulation of tumor necrosis factor-α induced by IL-6, whereas nitric oxide production was enhanced by Dex. Moreover, the enhancement of nitric oxide production could be demonstrated to be associated with stimulation of iNOS mRNA expression by the Dex treatment. (2) Cytotoxic activity of Mm1 cells on mouse B16 melanoma cells was much more enhanced by the co-treatment of IL-6 with Dex than IL-6 treatment alone. (3) Dex promoted further the suppression of proliferation induced by IL-6. (4) DNA fragmentation, introduced by the treatment of cells with IL-6, was further enhanced in the presence of Dex

Recovery from heat shock injury by activation of Na+-glucose cotransporter in renal epithelial cells

AbstractExposure of cells or organs to sublethal physical or chemical stresses induces disruption of cellular structures and functions. Here, we examined whether Na+-glucose cotransporter (SGLT1) is involved in the recovery from heat shock (HS) injury in porcine renal epithelial LLC-PK1 cells. Recovery from HS (42 °C for 3 h, then 37 °C for 12 h) increased SGLT1 activity, assessed by [14C]α-methyl glucopyranoside uptake, and a maximal transport rate (Vmax) from 2.4 to 5.9 nmol/mg protein/30 min, but did not alter an apparent affinity constant (Km). Protein distribution of SGLT1 in apical membrane fraction was also increased after recovery from HS without changing in total membrane fraction. Membrane integrity assessed by calcein accumulation was decreased by HS, and then returned to basal level. This recovery was inhibited by phloridzin, a potent SGLT1 inhibitor, and nonmetabolizable glucose analogues. Anti-transforming growth factor-β1 (TGF-β1) antibody inhibited both elevation of SGLT1 distribution in apical membrane and recovery of calcein accumulation induced by HS. Taken together, HS increases in the number of SGLT1 protein in apical membrane mediated via TGF-β1 signaling pathway. The increase of glucose uptake is necessary to repair plasma membrane integrity