title: Induction of IL-4 and IL-6 synthesis in vitro: variation in signaling requirements and kinetics are dependent on the anatomic source of the responding mononuclear cells.
abstract: We have shown differences in regulation of cytokine mRNA expression in human tonsil, spleen, and peripheral blood. After PHA stimulation of peripheral blood, IL-2, IL-4, and IL-6 mRNA were expressed with similar kinetics: peak expression occurred after four hours and subsequently declined over 48 hr. In PHA-stimulated splenic and tonsillar MNC, IL-2 and IL-6 mRNA were expressed later, with peak expression occurring after eight hours of stimulation and no mRNA detectable after 40 hr of stimulation. The intensity of the IL-6 mRNA signal and the amount of IL-6 secreted was much greater in MNC from peripheral blood than in spleen and tonsil and correlated with the percentage of monocytes in MNC from each tissue. IL-4 mRNA expression differed in all three tissues: PHA-stimulated tonsillar MNC expressed IL-4 mRNA with a major peak at eight hours and a minor peak at 24 hr after stimulation. The kinetics of mRNA were not due to effects of mixed cell populations. The same bimodal peak was observed in purified tonsillar T lymphocytes, and the minor 24-hr peak was dependent on IL-4 mRNA synthesis by cells expressing high amounts of VLA-beta 1 antigen (CDw29) on their surface and which lacked the CD45 epitope recognized by the mAb 2H4. Splenic MNC did not express IL-4 mRNA when stimulated with a number of mitogens and only exhibited IL-4 mRNA expression when stimulated with the combination of PHA and PMA or anti-CD3. Thus, IL-4 mRNA has markedly different kinetics and intensity of expression in spleen, peripheral blood, and tonsil.(ABSTRACT TRUNCATED AT 250 WORDS)
authors: Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
authors: H
authors: H
authors: Secrist
authors: V M
authors: VM
authors: Holers
authors: A
authors: A
authors: Levine
authors: M
authors: M
authors: Egan
authors: M H
authors: MH
authors: Nahm
authors: A W
authors: AW
authors: Butch
authors: M
authors: M
authors: Peters
mesh_terms: D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis / Q000378:metabolism; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000378:metabolism; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology
chemical_list: D007376:Interleukin-2; D015850:Interleukin-6; D012333:RNA, Messenger; D015847:Interleukin-4