PI3K limits TNF-<I>alpha</I> production in CD16-activated monocytes Export

@article{citeulike:4864575, abstract = {IgG complexes bind to Fc receptor family members FcgammaRI (CD64), FcgammaRII (CD32) and FcgammaRIII (CD16), activating cell MAPK and PI3K resulting in increased cytokine production from particular leukocytes. The signaling molecules involved in cytokine production after cross-linking CD16 have not been determined in monocytes. To address this question, TNF-alpha, IL-1beta and IL-6 were measured in activated monocytes after inhibiting MEK1/2, PI3K and glycogen synthase kinase-beta (GSK-3beta). The roles of GSK-3beta and NF-kappaB were then determined using reporter assays and siRNA treatment. The data suggested that an MAPK pathway stimulated TNF-alpha release but that active PI3K limited TNF-alpha, IL-1beta and IL-6 cytokine production after cross-linking CD16. PI3K was also shown to limit nuclear translocation of NF-kappaB. The limiting effect of PI3K on TNF-alpha production from activated monocytes depended on the decrease of GSK-3beta activity, which significantly reduced the transactivation of NF-kappaB. Moreover, the TNF-alpha production induced by CD16 cross-linking was reduced in monocytes after treatment with siRNA against NF-kappaB, implying that this transcription factor functioned in TNF-alpha production. The results suggest that CD16 cross-linking activated PI3K and that active PI3K limited TNF-alpha production by inhibiting GSK-3beta activity, that blocked the action of NF-kappaB.}, address = {Department of Biomedical Sciences, Baylor College of Dentistry, Texas A\&M Health Science Center, Dallas, TX, USA}, author = {Kramer, Phillip R. and Winger, Vanessa and Reuben, Jayne}, citeulike-article-id = {4864575}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/eji.200838801}, citeulike-linkout-1 = {http://www3.interscience.wiley.com/cgi-bin/abstract/121668193/ABSTRACT}, doi = {10.1002/eji.200838801}, issn = {1521-4141}, journal = {European Journal of Immunology}, keywords = {cd16, monocyte, pi3k, tnf}, month = {February}, number = {2}, pages = {561--570}, posted-at = {2009-06-16 03:11:17}, priority = {2}, title = {PI3K limits TNF-<I>alpha</I> production in CD16-activated monocytes}, url = {http://dx.doi.org/10.1002/eji.200838801}, volume = {39}, year = {2009} }

TY - JOUR ID - citeulike:4864575 L3 - citeulike-article-id:4864575 N2 - IgG complexes bind to Fc receptor family members FcgammaRI (CD64), FcgammaRII (CD32) and FcgammaRIII (CD16), activating cell MAPK and PI3K resulting in increased cytokine production from particular leukocytes. The signaling molecules involved in cytokine production after cross-linking CD16 have not been determined in monocytes. To address this question, TNF-alpha, IL-1beta and IL-6 were measured in activated monocytes after inhibiting MEK1/2, PI3K and glycogen synthase kinase-beta (GSK-3beta). The roles of GSK-3beta and NF-kappaB were then determined using reporter assays and siRNA treatment. The data suggested that an MAPK pathway stimulated TNF-alpha release but that active PI3K limited TNF-alpha, IL-1beta and IL-6 cytokine production after cross-linking CD16. PI3K was also shown to limit nuclear translocation of NF-kappaB. The limiting effect of PI3K on TNF-alpha production from activated monocytes depended on the decrease of GSK-3beta activity, which significantly reduced the transactivation of NF-kappaB. Moreover, the TNF-alpha production induced by CD16 cross-linking was reduced in monocytes after treatment with siRNA against NF-kappaB, implying that this transcription factor functioned in TNF-alpha production. The results suggest that CD16 cross-linking activated PI3K and that active PI3K limited TNF-alpha production by inhibiting GSK-3beta activity, that blocked the action of NF-kappaB. IS - 2 JF - European Journal of Immunology SN - 1521-4141 AD - Department of Biomedical Sciences, Baylor College of Dentistry, Texas A&M Health Science Center, Dallas, TX, USA EP - 570 TI - PI3K limits TNF-<I>alpha</I> production in CD16-activated monocytes VL - 39 SP - 561 KW - cd16 KW - monocyte KW - pi3k KW - tnf AU - Kramer, Phillip AU - Winger, Vanessa AU - Reuben, Jayne PY - 2009/02// UR - http://dx.doi.org/10.1002/eji.200838801 ER -