In order to examine the endoplasmic reticulum responses in macrophages, we stimulate macrophage cell line RAW 264.7 by LIPS. We found the phosphorylation of eukaryotic initiation factor eIF2 alpha and the expression of ATF4, GADD34, and GADD153 in RAW 264.7 cells in late time by the relatively large amount of LIPS stimulation. Unexpectedly LPS in the presence of ROS inhibitor N-acetyl-L-cysteine rapidly induced phosphorylation of eIF2 alpha and induction of GADD34 expression. We measured intra-cytoplasmic TNF alpha production in LPS stimulated RAW 264.7 cells. TNF alpha production induced by LPS stimulation was greatly suppressed by N-acetyl-L-cysteine. This suppression occurred relatively early, which correlated with early eIF2 alpha, phosphorylation indicating ER stress mediated shutoff of protein synthesis. (C) 2008 Elsevier Inc. All rights reserved.