TY - JOUR
T1 - Characterization of the inhibition of interleukin 2 mRNA accumulation by 12-O-tetradecanoylphorbol-13-acetate in primary lymphocytes
AU - Garlisi, C. G.
AU - Mastro, A. M.
PY - 1992
Y1 - 1992
N2 - We found previously that bovine lymph node cells (LNC) incubated with 12- O-tetradecanoylphorbol-13-acetate (TPA) for 18 h proliferate only to a limited degree on subsequent stimulation with concanavalin A (Con A), or with the comitogenic combination of Con A plus TPA. The lack of proliferation was traced to a lack of secretion of interleukin 2 (IL-2). Lack of secretion was paralled by a decrease in IL-2 mRNA levels. In this study we further characterized how TPA pretreatment affected IL-2 mRNA production. We found that TPA depressed IL-2 mRNA accumulation in a dose-dependent manner after at least 10 h of pretreatment. In contrast, pretreatment from 4 to 6 h augmented IL-2 mRNA accumulation. Furthermore, LNC stimulated with ionomycin plus TPA were less susceptible to inhibition by pretreatment with TPA, most likely because this mitogenic combination caused a much greater amount of IL-2 mRNA than did Con A or Con A plus TPA. Finally, a protein synthesis inhibitor, cycloheximide, partially counteracted the negative effects of TPA on IL-2 mRNA accumulation and on proliferation. These results suggest that TPA, probably acting through protein kinase C, initially augments the production of IL-2 mRNA but subsequently induces mechanisms to decrease the level of mRNA.
AB - We found previously that bovine lymph node cells (LNC) incubated with 12- O-tetradecanoylphorbol-13-acetate (TPA) for 18 h proliferate only to a limited degree on subsequent stimulation with concanavalin A (Con A), or with the comitogenic combination of Con A plus TPA. The lack of proliferation was traced to a lack of secretion of interleukin 2 (IL-2). Lack of secretion was paralled by a decrease in IL-2 mRNA levels. In this study we further characterized how TPA pretreatment affected IL-2 mRNA production. We found that TPA depressed IL-2 mRNA accumulation in a dose-dependent manner after at least 10 h of pretreatment. In contrast, pretreatment from 4 to 6 h augmented IL-2 mRNA accumulation. Furthermore, LNC stimulated with ionomycin plus TPA were less susceptible to inhibition by pretreatment with TPA, most likely because this mitogenic combination caused a much greater amount of IL-2 mRNA than did Con A or Con A plus TPA. Finally, a protein synthesis inhibitor, cycloheximide, partially counteracted the negative effects of TPA on IL-2 mRNA accumulation and on proliferation. These results suggest that TPA, probably acting through protein kinase C, initially augments the production of IL-2 mRNA but subsequently induces mechanisms to decrease the level of mRNA.
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M3 - Article
C2 - 1576243
AN - SCOPUS:0026534656
SN - 0277-6766
VL - 11
SP - 1
EP - 8
JO - Lymphokine and Cytokine Research
JF - Lymphokine and Cytokine Research
IS - 1
ER -