Jeong-Ho Seok

Methotrexate suppresses the interleukin-6 induced generation of reactive oxygen species in the synoviocytes of rheumatoid arthritis.

Various cytokines and reactive oxygen species (ROS) play a fundamental role in the inflammatory and immunologic processes of rheumatoid arthritis (RA). Methotrexate (MTX) is one of the disease-modifying anti-rheumatic drugs and its effect may be partly due to the modulation of immunologic or inflammatory reactions by some cytokines. In the present study, we investigated the effects of MTX on the gene expression and synthesis of interleukin-6 (IL-6), and the proliferative activity and the production of ROS in the fibroblast-like synoviocytes (FLSs) obtained from the patient of RA. The expression or production of IL-6 was induced spontaneously, and augmented by the addition of recombinant human IL-6 or recombinant human IL-1 beta and TNF-alpha in FLSs. These spontaneous and augmented IL-6 expressions or productions were suppressed by treatment with low-concentration of MTX (1 microg/ml). Also, IL-6 stimulated the proliferation of FLSs, and this IL-6 driven proliferation was inhibited with the treatment of MTX or N-acetylcysteine (NAC, 1 mM). Furthermore, ROS production in FLSs was increased significantly by IL-6, and its effect was also abrogated in the presence of MTX or NAC. These results suggest that inflammatory reaction in the synovium of RA patients could be augmented by the autocrine or other cytokine-induced production of IL-6 with subsequent generation of ROS in the synoviocytes, and the modulations of IL-6 synthesis and ROS production may contribute to the therapeutic effects of MTX for RA.

Aldosterone directly induces Na, K-ATPase α1-subunit mRNA in the renal cortex of rat

The change of blood pressure and the induction of Na, K‐ATPase α1‐subunit mRNA have been investigated in the renal cortex of aldosterone‐treated hypertensive rat. The increase of blood pressure by aldosterone‐treatment for 25 days was decreased by the treatment of amiloride or spironolactone. The level of Na, K‐ATPase α1‐subunit mRNA of the renal cortex in aldosterone‐treated rat was increased than that in the control, and its increase was repressed by treatment of spironolactone, but not altered by the treatment of amiloride. This result suggests that the increase of Na, K‐ATPase α1‐subunit mRNA in the renal cortex of aldosterone‐treated hypertensive rat may be related with the direct induction of Na, K‐ATPase mRNA without the increase of Na‐traffic through Na‐channel.

Regulation of Na,K‐ATPase activity in renal basolateral membrane of 1‐clip‐1‐kidney hypertensive rat

The changes of Na,K‐ATPase activity and its regulation have been investigated in the renal cortex of 1‐clip‐1‐kidney hypertensive rat. Ouabain‐sensitive Na,K‐ATPase activity (Emax) and [3H]ouabain‐binding site (Bmax) in the hypertensive rat were slightly increased than those in the control. The levels of Na,K‐ATPase α1‐ and β1‐subunit mRNA of the renal cortex in hypertensive rat were more increased than those in the control. Their increases were repressed by actinomycin‐D, but not altered or more increased by cycloheximide. These results suggest that the increase of Na,K‐ATPase activities and ouabain binding sites in 1‐clip‐1‐kidney hypertensive rat may be correlated with the increases of gene expression in transcription level and/or of mRNA stability of Na,K‐ATPase.