p38 MAPK plays a role in IL-4 synthesis in jacalin plus CD28-stimulated CD4+ T cells--II.
We have previously shown that jacalin, a CD4+ T cell lectin, induces phosphorylation of intracellular events, moderate levels of interleukin (IL)-2 secretion. We have also shown that in the presence of CD28 costimulation, jacalin induces IL-4 secretion. In the present study, we showed that stimulation of normal CD4+ T cells with jacalin plus CD28 cross-linking (CD28XL) resulted in phosphorylation of signal transducer and activator of transcription (STAT)-6 and expression of Bcl-2 and Bcl-xL, which were inhibited significantly when cells were cultured in the presence of the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580. We further generated jacalin-induced CD4+ T cell blasts, examined the effects of CD28XL, and observed enhanced up-regulation of p38 and activation of STAT-6, Bcl-2, and Bcl-xL. Engagement of CD28 alone induced a marked degree of phosphorylation of p38 MAPK and IL-4 secretion in memory T cells (jacalin blasts), whereas in naïve T cells, jacalin plus CD28XL was required to induce these molecules. Incubation of cells with p38 inhibitor prior to CD28XL resulted in down-modulation of all these molecules. Further treatment with IL-4 has not reversed this trend. Our studies imply that p38 MAPK may play an important role in induction of these molecules and a putative role in protecting cells from undergoing apoptosis.
Department of Biomedical Sciences, C. W. Post Campus, Long Island University, 720 Northern Blvd., Brookville, NY 11548, USA. stamma@liu.edu
Seetha M Lakshmi
SM
Tamma
Kun Wook
KW
Chung
Tejal
T
Patel
Satya Priya
SP
Balan
Savita
S
Pahwa
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018106:CD28 Antigens / Q000276:immunology / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D019254:Genes, bcl-2; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007156:Immunologic Memory; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D037121:Plant Lectins / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011725:Pyridines / Q000494:pharmacology; D050800:STAT6 Transcription Factor / Q000096:biosynthesis / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics; D051020:bcl-X Protein / Q000096:biosynthesis / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*
D000911:Antibodies, Monoclonal; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D018106:CD28 Antigens; D007093:Imidazoles; D037121:Plant Lectins; D019253:Proto-Oncogene Proteins c-bcl-2; D011725:Pyridines; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C043696:jacalin; D015847:Interleukin-4; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580