Impaired interleukin-2 production in active ulcerative colitis is reversed by calcium ionophore plus phorbol myristate acetate and related to altered intracellular Ca2+ responses.
Phytohemagglutin in (PHA)-induced IL-2 production in vitro by peripheral blood mononuclear cells (PBMC) and lamina propria mononuclear cells (LPMC) from patients with active UC (n = 24, n = 8, respectively) was significantly less than that in controls (n = 13, n = 8, respectively) and inactive patients (n = 11). In contrast, PBMC from inactive disease showed no significant difference when compared with the controls. Depressed IL-2 production in active UC was not reversed by the addition of anti-CD3 monoclonal antibody plus phorbol myristate acetate (PMA), but was largely reversed by adding calcium ionophore plus PMA. Using a fluorescent Ca2+ probe fura-2, we found that after PHA stimulation LPMC from patients with active UC showed a lower magnitude of rise in intracellular free calcium concentration ([Ca2+]i) than control cells. These results suggest that impaired PHA-induced IL-2 production in active UC may be related to some alterations of the early signaling events that cause elevation of the [Ca2+]i.
Kuroiwa
A
A
First Department of Internal Medicine, Nagoya University School of Medicine.
Kusugami
K
K
Shinoda
M
M
Haruta
J
J
Morise
K
K
D000328:Adult; D000368:Aged; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000378:metabolism*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*; D007424:Intracellular Fluid / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D007376:Interleukin-2; D016853:Muromonab-CD3; D010835:Phytohemagglutinins; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium