Cutting edge: calcium/calmodulin-dependent protein kinase type IV is essential for mesangial cell proliferation and lupus nephritis

K Ichinose, T Rauen, YT Juang, K Kis-Toth… - The Journal of …, 2011 - journals.aai.org
K Ichinose, T Rauen, YT Juang, K Kis-Toth, M Mizui, T Koga, GC Tsokos
The Journal of Immunology, 2011journals.aai.org
Renal involvement in systemic lupus erythematosus remains a major cause of morbidity and
mortality. Although immune parameters that instigate renal damage have been
characterized, their link to local processes, which execute tissue damage, is poorly
understood. Using genetic-deletion and pharmacological-inhibition approaches, we
demonstrated that calcium/calmodulin-dependent protein kinase type IV, which contributes
to altered cytokine production in systemic lupus erythematosus patients, controls …
Abstract
Renal involvement in systemic lupus erythematosus remains a major cause of morbidity and mortality. Although immune parameters that instigate renal damage have been characterized, their link to local processes, which execute tissue damage, is poorly understood. Using genetic-deletion and pharmacological-inhibition approaches, we demonstrated that calcium/calmodulin-dependent protein kinase type IV, which contributes to altered cytokine production in systemic lupus erythematosus patients, controls spontaneous and platelet-derived growth factor-stimulated mesangial cell proliferation and promotes IL-6 production through AP-1. Our studies identified calcium/calmodulin-dependent protein kinase type IV as a valuable treatment target for lupus nephritis and point out the importance of local kidney factors in the expression of tissue damage that, if properly targeted, should enhance clinical benefit and limit toxicity.
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