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Jennifer E Towne, Blair R Renshaw, Jason Douangpanya, Brian P Lipsky, Min Shen, Christopher A Gabel, John E Sims
IL-36α, IL-36β, and IL-36γ (formerly IL-1F6, IL-1F8, and IL-1F9) are IL-1 family members that signal through the IL-1 receptor family members IL-1Rrp2 (IL-1RL2) and IL-1RAcP. IL-36Ra (formerly IL-1F5) has been reported to antagonize IL-36γ. However, our previous attempts to demonstrate IL-36Ra antagonism were unsuccessful. Here, we demonstrate that IL-36Ra antagonist activity is dependent upon removal of its N-terminal methionine. IL-36Ra starting at Val-2 is fully active and capable of inhibiting not only IL-36γ but also IL-36α and IL-36β...
December 9, 2011: Journal of Biological Chemistry
Hal Blumberg, Huyen Dinh, Charles Dean, Esther S Trueblood, Keith Bailey, Donna Shows, Narasimharao Bhagavathula, Muhammad Nadeem Aslam, James Varani, Jennifer E Towne, John E Sims
Psoriasis is a common immune-mediated disease in European populations; it is characterized by inflammation and altered epidermal differentiation leading to redness and scaling. T cells are thought to be the main driver, but there is also evidence for an epidermal contribution. In this article, we show that treatment of mouse skin overexpressing the IL-1 family member, IL-1F6, with phorbol ester leads to an inflammatory condition with macroscopic and histological similarities to human psoriasis. Inflammatory cytokines thought to be important in psoriasis, such as TNF-α, IL-17A, and IL-23, are upregulated in the mouse skin...
October 1, 2010: Journal of Immunology: Official Journal of the American Association of Immunologists
Ravisankar A Ramadas, Susan L Ewart, Benjamin D Medoff, Ann Marie LeVine
Interleukin-1 (IL-1) is a proinflammatory cytokine that signals through the Type I IL-1 receptor (IL-1RI). Novel IL-1-like cytokines were recently identified. Their functions in lung disease remain unclear. Interleukin-1 family member-9 (IL-1F9) is one such IL-1-like cytokine, expressed in the lungs of humans and mice. IL-1F9 signals through IL-1 receptor-related protein 2 (IL-1Rrp2/IL-1RL2), which is distinct from IL-1RI. We sought to determine if IL-1F9 acts as a proinflammatory cytokine in lung disease. IL-1F9 protein was increased in lung homogenates of house dust mite-challenged A/J mice compared with controls, and expression was seen in airway epithelial cells...
February 2011: American Journal of Respiratory Cell and Molecular Biology
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