[Molecular mechanism of cytokine gene expression in Th1 and Th2].
Upon activation by antigens, helper T cells differentiate into one of several subsets, characterized by their distinct cytokine-production patterns. Among these subsets, Th1 cells are known to activate cellular immunity resulting in inflammatory response, whereas Th2 cells induce humoral and allergic responses and suppress inflammation. Th1 and Th2 effector functions and their development are attributable to their distinct cytokine expression patterns. Recent reports have demonstrated that differential expression of cell surface molecules, such as adhesion molecule and chemokine receptor, is involved in their recruitment into target tissues. It is, therefore, suggested that clarification of the mechanisms of differential gene expression in Th1/Th2 should lead to rational strategies for manipulating pathological immune responses. Activation of helper T cells mediated by the T cell receptor induces a series of biochemical events. Among them, both the activation of PKC/Ras- and CaM/CN-mediated pathways play a central role in the signal transduction of cytokine gene expression. Closer examination using non-transformed murine Th1 and Th2 clones suggested that a balance between the activities of the two signaling pathways contributes to cytokine gene expression. We propose that one of the targets of PGE2, whose effect distinguishes Th1 from Th2, resides in the downstream PKC/Ras-mediated pathway.
Naito
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Department of Anesthesia, Kobe Cite General Hospital.
D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D016207:Cytokines / Q000235:genetics*; D015232:Dinoprostone / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology / Q000502:physiology*; D018418:Th2 Cells / Q000276:immunology / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism
D017252:CD3 Complex; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D015232:Dinoprostone