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These results suggest that corticosteroid treatment in asthma can reduce the lamina reticular thickness by modulation of IGF-I expression with consequent inhibition of the airway infiltration by inflammatory cells, and therefore may help to prevent remodelling of the airways.

Diabetic nephropathy is a leading cause of morbidity and mortality in diabetes mellitus. Since diabetic glomerulopathy is characterized by an expansion of glomerular mesangium that eventually progresses to obliterate the capillary lumen, mesangial cells (MCs) are thought to play a central role in the pathogenesis of diabetic nephropathy. Elevated glucose levels appear to initiate MC dysfunction, probably via metabolic abnormalities such as derangements in polyol pathway [1], increased activity of protein kinase C (PKC) [2,3], and increased production of transforming growth factor-b (TGF-b) [4]. However, the interaction between these metabolic abnormalities is unclear. To clarify this, we investigated whether inhibition of the polyol pathway by an aldose reductase inhibitor (ARI) could prevent the glucose-induced increase in the production of TGF-b and the activity of PKC in cultured human MCs. Materials and methodsHuman MCs were cultured as previously reported [5]. A single cell line between the third and eighth passages was employed in this study. RPMI-1640 medium (GIBCO BRL, Gaithersburg, Md., USA) containing 20 % fetal calf serum (FCS) was supplemented with either 5 or 33 mmol/l glucose in the presence (10 ±8~5 10 ±5 mol/l) or absence of epalrestat. Medium supplemented with 5 mmol/l glucose + 28 mmol/l mannitol was used as an osmotic control. Since our preliminary experiments showed that incubating MCs with 33 mmol/l glucose for 6 days resulted in a greater increase in TGF-b proDiabetologia (1998) 41: 362±364 Rapid communicationAn aldose reductase inhibitor prevents glucose-induced increase in transforming growth factor-b and protein kinase C activity in cultured human mesangial cells Summary We investigated the effect of inhibition of a polyol pathway on the glucose-induced increase in transforming growth factor-b (TGF-b) production and activity of protein kinase C (PKC) in cultured human mesangial cells (MCs). The exposure of MCs to 33 mmol/l glucose resulted in an increase in TGF-b production, measured by ELISA, compared with 5 mmol/l glucose. The glucose-induced increase in TGF-b was prevented by concomitant incubation with epalrestat, an aldose reductase inhibitor (ARI), in a dose-dependent manner at a concentration of more than 10 ±6 mol/l. Moreover, the glucose-induced enhancement of PKC activity in the membrane fraction of MCs was also abolished by epalrestat. The addition of epalrestat to MCs cultured with 5 mmol/l glucose showed no demonstrable effects on TGF-b production and PKC activity. These results provide direct evidence for linkages between derangements in polyol pathway and glucose-induced overproduction of TGF-b and enhancement of PKC activity in MCs. Accordingly, the effect of an ARI on these metabolic abnormalities in MCs may justify its clinical application for treatment of diabetic nephropathy.[ Diabetologia (1998) 41: 362±364]

Thrombospondin (TSP) is a multifunctional glycoprotein that is synthesized by a variety of cells including mesangial cells (MCs). To clarify the effect of TSP on the pathogenesis of diabetic nephropathy, we studied the effect of glucose concentrations on TSP synthesis in cultured human MCs. Thereafter, the effects of TSP on the activation of transforming growth factor beta (TGF-β) and fibronectin production were investigated in MCs. Incubating MCs with elevated glucose levels for 6 days resulted in an increase in TSP synthesis, measured by an enzyme-linked immunosorbent assay, both in culture media and cell layers. Treatment of MCs with TSP (final concentrations 1 and 5 µg/ml) for 24 h resulted in an increase (1.3- and 2.1-fold, respectively) in active TGF-β, which was determined with an enzyme-linked immunosorbent assay using TGF-β-soluble receptor type II, in the culture media without having any effect on the production of total TGF-β. Exposure of MCs to TSP caused enhancement of fibronectin production in both media and cell layers in a TSP dose-dependent manner with the maximum at a TSP concentration of 1 µg/ml. The TSP-induced increase in fibronectin production from MCs was completely prevented by concomitant treatment with 10 µg/ml anti-TGF-β neutralizing antibody. These results indicate that the TSP production is promoted by a high ambient glucose concentration in human MCs and that TSP, in turn, causes an increase in fibronectin production via activation of TGF-β.

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