Nobuki Arai

Reactive oxygen intermediates stimulate interleukin-6 production in human bronchial epithelial cells

Reactive oxygen intermediates (ROIs) play an important role in the initiation and progression of lung diseases. In this study, we investigated whether ROIs were involved in the induction of interleukin (IL)-6 in human bronchial epithelial cells. We exposed normal human bronchial epithelial cells as well as a human bronchial epithelial cell line, HS-24, to ROIs. We measured the amount of IL-6 in the culture supernatants using ELISA and the IL-6 mRNA levels using RT-PCR. Superoxide anions (O-2), but not hydrogen peroxide (H2O2), increased IL-6 production. To examine whether it is a cell type-specific mechanism of airway epithelial cells, the experiments were also performed in human lung fibroblasts, WI-38-40. In WI-38-40 cells, neither O-2 nor H2O2 increased IL-6 production. In contrast, tumor necrosis factor (TNF)-alpha (200 U/ml) induced IL-6 at the protein and mRNA levels in both airway epithelial cells and lung fibroblasts. This cytokine-induced IL-6 production was significantly suppressed by several antioxidants, including dimethyl sulfoxide (DMSO), in airway epithelial cells. In WI-38-40 cells, DMSO was not able to suppress IL-6 production induced by TNF-alpha. Pretreatment with DMSO recovered the TNF-alpha-induced depletion of intracellular reduced glutathione in HS-24 cells. These findings indicate that oxidant stress specifically induces IL-6 production in human bronchial epithelial cells and that in these cells ROIs may be involved in IL-6 production after stimulation with cytokines such as TNF-alpha. Presumably, ROIs participate in the local immune response in lung diseases via IL-6 release from bronchial epithelial cells.

Serum Interleukin-6 Level is a Sensitive Parameter of Disease Activity in Rheumatoid Arthritis.

In rheumatoid synovium, interleukin-6 (IL-6) is the most abundantly expressed cytokine. Therefore, we investigated whether serum IL-6 levels could be clinically useful parameters of disease activity in rheumatoid arthritis (RA). The serum IL-6 levels were measured by enzyme-linked immunosorbent assay. The IL-6 levels were significantly higher in sera from patients with RA (n = 108, 13.3 ± 14.0 pg/mL) than in those from the normal controls (n = 10, < 3.13 pg/mL). The IL-6 levels significantly correlated with conventional parameters, such as the Lansbury index, joint score, erythrocyte sedimentation rates, and C-reactive protein. In addition, the serum IL-6 level was useful to determine clinical remission. Advantages of serial measurement of IL-6 were observed in two cases. These findings suggested that the serum IL-6 level may be clinically useful as a sensitive parameter of disease activity in RA.

Ionizing radiation suppresses FAP-1 mRNA level in A549 cells via p53 activation

Ionizing radiation (IR) is known to upregulate cell surface Fas through p53 activation in various cells. However, the signaling pathway intermediating between p53 activation and cell surface Fas upregulation remains to be elucidated. Recently, Fas‐associated phosphatase‐1 (FAP‐1) has been reported to associate with Fas and inhibit cell surface Fas expression. We evaluated the expression of FAP‐1 mRNA following IR in A549 cells. Ionizing radiation inhibited the expression of FAP‐1 mRNA. Pretreatment with p53 inhibitor pifithrin α cancelled the IR‐induced downregulation of FAP‐1 mRNA. These results suggest that IR‐induced p53 activation may upregulate cell surface Fas via the down‐modulation of FAP‐1.

Syndrome of inappropriate secretion of antidiuretic hormone associated with amyotrophic lateral sclerosis in respiratory failure

A 65‐year‐old man who had muscle weakness and dysarthria was admitted for investigation of motor neuron disease. He had lost 12 kg of weight in 6 months. Neurological findings disclosed upper and lower motor neuron disturbances with normal sensory nerve function, and needle electromyography showed a neurogenic pattern. Laboratory findings on admission demonstrated dilutional hyponatraemia due to an excessive secretion of antidiuretic hormone (ADH). Based on these findings, the patient was diagnosed as having the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with amyotrophic lateral sclerosis (ALS). During the night of first hospital day, the patient complained of severe dyspnoea, and mechanical ventilation was commenced. Following the mechanical ventilation, plasma ADH levels and serum sodium concentration were normalized. We propose that respiratory failure secondary to the atrophy of respiratory muscle might be responsible for the development of SIADH.