Silicon Investor (SI) -- The First Internet Community

STOCKTALK

We've detected that you're using an ad content blocking browser plug-in or feature. Ads provide a critical source of revenue to the continued operation of Silicon Investor. We ask that you disable ad blocking while on Silicon Investor in the best interests of our community. If you are not using an ad blocker but are still receiving this message, make sure your browser's tracking protection is set to the 'standard' level.

Biotech / Medical : ZymoGenetics ZGEN -- Ignore unavailable to you. Want to Upgrade?

To: tuck who wrote (130)	6/5/2008 2:36:41 PM
From: tuck	Read Replies (1) \| Respond to of 210

[IL-21 mediates apoptosis through up-regulation of the BH3 family member BIM and enhances both direct and antibody-dependent cellular cytotoxicity in primary chronic lymphocytic leukemia cells in vitro] >>Blood. 2008 May 1;111(9):4723-30. Epub 2008 Jan 8. IL-21 mediates apoptosis through up-regulation of the BH3 family member BIM and enhances both direct and antibody-dependent cellular cytotoxicity in primary chronic lymphocytic leukemia cells in vitro. Gowda A, Roda J, Hussain SR, Ramanunni A, Joshi T, Schmidt S, Zhang X, Lehman A, Jarjoura D, Carson WE, Kindsvogel W, Cheney C, Caligiuri MA, Tridandapani S, Muthusamy N, Byrd JC. Division of Hematology-Oncology, Department of Medicine, The Ohio State University, Columbus, USA. Interleukin-21 (IL-21) is a recently identified gamma-chain receptor cytokine family member that promotes B-cell apoptosis as well as activation of innate immune system. Based on this, we hypothesized that IL-21 might enhance the apoptosis induced by fludarabine and rituximab and also play a role in augmenting immune-mediated clearance of the chronic lymphocytic leukemia (CLL) cells. Our studies demonstrate that the majority of CLL patients have surface IL-21 receptor-alpha, and its expression correlates with apoptosis, tyrosine phosphorylation of STAT1, and up-regulation of the proapoptotic BH3 domain protein BIM. IL-21-induced BIM up-regulation is critical for apoptosis because inhibition of BIM expression using small interfering RNA prevented IL-21-induced apoptosis. IL-21 treatment of CLL cells but not normal T cells with fludarabine or rituximab additively enhanced the direct cytotoxic effect of these therapies. In addition to its proapoptotic effect, IL-21 promoted STAT1 and STAT5 phosphorylation in natural killer cells with concurrent enhanced antibody-dependent cellular cytotoxicity against rituximab-coated CLL cells in vitro. These data provide justification for combination studies of IL-21 with fludarabine and rituximab in CLL and suggest that BIM up-regulation might serve as relevant pharmacodynamic end point to measure biologic effect of this cytokine in vivo.<< Actually, ZGEN's publications page is updated pretty quickly, so it's also a good resource: zymogenetics.com Cheers, Tuck

To: tuck who wrote (130)	5/10/2009 1:13:12 PM
From: tuck	Read Replies (2) \| Respond to of 210

[IL-21 Is Required to Control Chronic Viral Infection.] >>Science. 2009 May 7. [Epub ahead of print] IL-21 Is Required to Control Chronic Viral Infection. Elsaesser H, Sauer K, Brooks DG. Department of Microbiology, Immunology and Molecular Genetics and the UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. CD4(+) and CD8(+) T cell functions are rapidly aborted during chronic infection, preventing viral clearance. CD4(+) T cell help is required throughout chronic infection to sustain CD8 T cell responses; however, the necessary factor(s) provided by CD4(+) T cells are currently unknown. Using a mouse model of chronic viral infection, we demonstrate that interleukin-21 (IL-21) is an essential component of CD4(+) T cell help. In the absence of IL-21 signaling, despite elevated CD4(+) T cell responses, CD8(+) T cell responses are severely impaired. CD8(+) T cells directly require IL-21 to avoid deletion, maintain immunity, and resolve persistent infection. Thus, IL-21 specifically sustains CD8(+) T cell effector activity and provides a mechanism of CD4(+) T cell help during chronic virus infection.<< Cheers, Tuck