Kooijman Ron, Coppens Astrid, Hooghe-Peters Elisabeth
Laboratory for Neuroendocrine Immunology, Department of Pharmacology, Medical School, Free University of Brussels (VUB), Laarbeeklaan 103, B-1090 Brussels, Belgium.
Cell Signal. 2003 Dec;15(12):1091-8. doi: 10.1016/s0898-6568(03)00069-x.
Interleukin (IL)-8 serves as a major chemoattractant for neutrophils and has also been proposed to affect cancer progression. In the present study, we show that IGF-I stimulates IL-8 mRNA expression and IL-8 secretion in the leukemic cell line HL-60. Stimulation of IL-8 expression was completely attenuated by two inhibitors of mitogen-activated protein kinase (MAPK) kinase (MEK), which phosphorylates the MAPKs extracellular-regulated kinase (ERK)1 and ERK2, and by the c-Jun NH2-terminal kinase (JNK) inhibitor SP600125. In contrast, inhibitors of p38 MAPK and phosphatidylinositol-3 kinase (PI3K) did not abrogate the effect of IGF-I. We also show that IGF-I stimulates the activation of ERK1 and ERK2, but we could not detect any effect of IGF-I on the phosphorylation of p38, JNK(p46) or JNK(p54). Collectively, our results suggest that basal JNK activity and activation of the MEK-ERK pathway are required for upregulation of IL-8 by IGF-I in HL-60 cells.
白细胞介素（IL）-8是中性粒细胞的主要趋化因子，也被认为会影响癌症进展。在本研究中，我们发现胰岛素样生长因子-I（IGF-I）可刺激白血病细胞系HL-60中IL-8 mRNA的表达及IL-8的分泌。促分裂原活化蛋白激酶（MAPK）激酶（MEK，可使MAPK细胞外调节激酶（ERK）1和ERK2磷酸化）的两种抑制剂以及c-Jun氨基末端激酶（JNK）抑制剂SP600125可完全减弱IL-8的表达刺激。相反，p38 MAPK抑制剂和磷脂酰肌醇-3激酶（PI3K）抑制剂并不能消除IGF-I的作用。我们还发现IGF-I可刺激ERK1和ERK2的激活，但未检测到IGF-I对p38、JNK（p46）或JNK（p54）磷酸化有任何影响。总体而言，我们的结果表明，基础JNK活性以及MEK-ERK途径的激活是IGF-I上调HL-60细胞中IL-8所必需的。
