TY - JOUR
T1 - IL-4 inhibits the costimulatory activity of IL-2 or picolinic acid but not of lipopolysaccharide on IFN-γ-treated macrophages
AU - Cox, George W.
AU - Chattopadhyay, Utpala
AU - Oppenheim, Joost J.
AU - Varesio, Luigi
PY - 1991/12/1
Y1 - 1991/12/1
N2 - We reported previously that IL-2 induces tumoricidal activity in IFN-γ-treated murine macrophages. The present study was performed to investigate the regulation of IL-2-dependent tumoricidal activity in murine macrophage cell lines. The v-raf/v-myc-immortalized murine macrophage cell lines ANA-1, GG2EE, and HEN-CV did not express constitutive levels of cytotoxic activity against P815 mastocytoma cells. Moreover, these macrophage cell lines did not become tumoricidal after exposure to IL-4, IFN-γ, IL-2 or LPS. However, these macrophages developed cytotoxic capabilities after incubation with either IFN-γ plus IL-2 or IFN-γ plus LPS. IL-4 inhibited IFN-γ plus IL-2- but not IFN-γ plus LPS-induced tumoricidal activity. This effect of IL-4 was not restricted to v-raf/v-myc-immortalized macrophage cell lines because similar results were obtained by using a macrophage cell line that was established from a spontaneous histiocytic sarcoma. The suppressive activity of IL-4 on the ANA-1 macrophage cell line was dose-dependent (approximately 12-200 U/ml) and was neutralized by the addition of anti-IL-4 mAb. IL-4 decreased the IFN-γ-induced expression of mRNA for the p55 (α) subunit of the IL-2R in ANA-1 macrophages. Therefore, at least one mechanism by which IL-4 may have inhibited IFN-γ plus IL-2-induced tumoricidal activity was by reducing macrophage IL-2Rα mRNA expression. We have previously reported that picolinic acid, a tryptophan metabolite, is a costimulator of macrophage tumoricidal activity. We now report that IL-4 also inhibited IFN-γ plus picolinic acid-induced cytotoxicity in ANA-1 macrophages. We propose that IL-2 and picolinic acid may have a common mechanism of action that is susceptible to IL-4 suppression.
AB - We reported previously that IL-2 induces tumoricidal activity in IFN-γ-treated murine macrophages. The present study was performed to investigate the regulation of IL-2-dependent tumoricidal activity in murine macrophage cell lines. The v-raf/v-myc-immortalized murine macrophage cell lines ANA-1, GG2EE, and HEN-CV did not express constitutive levels of cytotoxic activity against P815 mastocytoma cells. Moreover, these macrophage cell lines did not become tumoricidal after exposure to IL-4, IFN-γ, IL-2 or LPS. However, these macrophages developed cytotoxic capabilities after incubation with either IFN-γ plus IL-2 or IFN-γ plus LPS. IL-4 inhibited IFN-γ plus IL-2- but not IFN-γ plus LPS-induced tumoricidal activity. This effect of IL-4 was not restricted to v-raf/v-myc-immortalized macrophage cell lines because similar results were obtained by using a macrophage cell line that was established from a spontaneous histiocytic sarcoma. The suppressive activity of IL-4 on the ANA-1 macrophage cell line was dose-dependent (approximately 12-200 U/ml) and was neutralized by the addition of anti-IL-4 mAb. IL-4 decreased the IFN-γ-induced expression of mRNA for the p55 (α) subunit of the IL-2R in ANA-1 macrophages. Therefore, at least one mechanism by which IL-4 may have inhibited IFN-γ plus IL-2-induced tumoricidal activity was by reducing macrophage IL-2Rα mRNA expression. We have previously reported that picolinic acid, a tryptophan metabolite, is a costimulator of macrophage tumoricidal activity. We now report that IL-4 also inhibited IFN-γ plus picolinic acid-induced cytotoxicity in ANA-1 macrophages. We propose that IL-2 and picolinic acid may have a common mechanism of action that is susceptible to IL-4 suppression.
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M3 - Article
C2 - 1940368
AN - SCOPUS:0025748799
VL - 147
SP - 3809
EP - 3814
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 11
ER -