IL-4 augments anisomycin-induced p38 activation via Akt pathway in a follicular dendritic cell (FDC)-like line.
Follicular dendritic cells (FDCs) play pivotal roles in germinal center (GC) responses in secondary lymphoid follicles, and their functions are influenced by cytokines present in the GC. We investigated the functional effects of interleukin-4 (IL-4) using an established FDC-like line of HK cells. In spite of the activation of ERK1/2 and PI3K/Akt pathways by IL-4, which are implicated in the induction of cell proliferation and survival, IL-4 did not exhibit protective function on anisomycin-induced apoptosis of HK cells, but rather slightly enhanced it. This IL-4 effect correlated with the up-regulation of anisomycin-induced p38 signaling, which is attenuated by inhibition of the PI3K/Akt pathway. Expression of an active form of Akt increased anisomycin-elicited activation of p38 and its upstream kinase MKK3/6. Our data indicate a positive cross-talk between the p38 and PI3K/Akt pathways.
Lee
Hyang-Mi
HM
Department of Biology and Protein Network Research Center, Yonsei University, 134 Shinchon-dong, Seodaemoon-gu, Seoul 120-749, South Korea.
Jin
Hyung-Sung
HS
Park
Jae-Won
JW
Park
Sun-Mi
SM
Jeon
Hye-Kyung
HK
Lee
Tae H
TH
D000841:Anisomycin / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D020566:Dendritic Cells, Follicular / Q000166:cytology* / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D020239:Receptor Cross-Talk; D015398:Signal Transduction; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases
D011500:Protein Synthesis Inhibitors; D011518:Proto-Oncogene Proteins; D015847:Interleukin-4; D000841:Anisomycin; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases