THURSDAY, Dec. 27 (HealthDay News) -- Inhibiting downstream signaling through the interferon-α receptor may reduce the inflammatory response in a mouse model of systemic lupus erythematosus, according to a report published online Dec. 16 in Nature Immunology.
Lu Wang, Ph.D., from the Hospital for Special Surgery in New York City, and colleagues examined the function of the calcium-dependent kinases CaMK and Pyk2 in signaling through immunoreceptor tyrosine-based activation motif (ITAM)-coupled receptors. The role of CaMK and Pyk2 were examined in interferon-α signaling in the spleen, lymph nodes and kidneys in a mouse model of systemic lupus erythematosus, an autoimmune disease where type I interferons have been linked to pathogenesis.
The researchers found that CaMK and Pyk2 were involved in signaling through integrins and an ITAM-containing adaptor, and involved in augmenting Jak-1 activation and STAT1-dependent gene expression induced by interleukin-10 and interferon-α. In the mouse lupus model, interferon-α induced phosphorylation of STAT1, which was suppressed by a CaMK inhibitor.
"Inhibition of CaMK and Pyk2 diminished the STAT1-mediated inflammatory effects of interferons, including in vivo in a mouse model of the interferon-driven disease systemic lupus erythematosus," Wang and colleagues conclude. "Thus, CaMK and Pyk2 may be therapeutic targets whose inhibition downregulates the inflammatory properties of cytokines."
Abstract
Full Text (subscription or payment may be required)
