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?patho-genesis?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,?chem-okines?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-α),?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.