Interleukin-13 inhibits cytokines synthesis by blocking nuclear factor-κB and c-Jun N-terminal kinase in human mesangial cells

Objective： Monocytes/macrophages, proinflammatory cytokines and chemokines are important in the pathogenesis of glomerulonephritis. Interleukin （IL） -13 has been shown to exert potent anti-inflammatory properties. This study was designed to investigate the effect of IL-13 on the expression of proinflammatory cytokines, chemokines and profibrogenic cytokines and the involved molecular mechanism in cultured human mesangial cells （HMCs）. Methods： The expressions of proinflammatory cytokines, chemokines and profibrogenic cytokines were determined by ribonuclease protection assay （RPA）. Activity of nuclear factor-kappa B （NF-κB） and activa- tor protein-1 （AP-1） was examined by electrophoretic mobility shift assay （EMSA）. NF-κB subunit p65 nuclear transportation and c-Jun N-terminal kinase （JNK） activity were assayed by immunoblot. Results： Recombinant IL-13 inhibited tumor necrosis factor-α （TNF-u）, IL-1α, IL-1β, monocyte chemoattractant protein-1 （MCP-1）, IL-8, and transforming growth factor-β1 （TGF-β1） mRNA expressions in a dose-dependent manner. Lipopoly- sacchorides （LPS） dramatically increased NF-κB DNA binding activity of HMCs, which was inhibited by IL-13 in a dose-dependent manner. LPS-activated NF-κB contained p50 and p65 dimers, but not c-Rel subunit. IL-13 blocked LPS-induced NF-κB subunit p65. LPS stimulated JNK/AP-1 activation, which was inhibited by IL-13 in a dose-dependent manner. Conclusion： IL-13 inhibits proinflammatory cytokines, chemokines, and profibrogenic cytokines synthesis by blocking NF-κB and JNK/AP-1 activation. These observations point to the importance of IL-13 in the modulation of inflammatory processes in the renal glomerulus.

CONGENITAL DISLOCATION OF THE HIP AND JOINT LAXITY

The authors reviewed 200 normal children and 225 cases of congenitaldislocation of the hip (CDH), all below 5 years of age. These cases were checked at thehip, ankle, elbow, wrist and knee for hyper-extension and thumb-radius angle at the wrist.From the values of 200 normal cases, SD was derived. Joint laxity was graded by the fol-lowing method (Wynne Davies, Tsuyama). SD±2=2 points, SD±1=1 point,【SD=0point. The result showed that in the normal group there were 8-12% of joint laxity,whereas in the CDH group there were 34-46%. Dividing the CDH and normal groups in-to boys and girls, and those below 2 and those aged 2-5 years group (50 each), itshowed a P value of 【0.01, 【0.02, 【0.01 and 【0.001 respectively. The authors believedthat CDH has a congenital fibrous tissue defect, probably associated with abnormality ofthe collagen fibres. The authors discuss this with clinical problems.