Abnormal interleukin 10Ralpha expression contributes to the maintenance of elevated cyclooxygenase-2 in non-small cell lung cancer cells.

Abstract

Non-small cell lung cancer (NSCLC) cells are known to constitutively overexpress cyclooxygenase (COX)-2. Tumor COX-2-dependent production of PGE(2) triggers the synthesis of lymphocyte and macrophage interleukin (IL)-10 that, in turn, is known to potently suppress COX-2 in normal cells. Thus, we investigated the capacity of IL-10 to down-regulate COX-2 expression in NSCLC cells. Western blotting and ELISA analyses revealed that IL-10 did not affect COX-2 expression and subsequent PGE(2) production in NSCLC cells. Although normal human bronchial epithelial cells expressed both intracellular and membrane IL-10Ralpha, NSCLC cells only expressed intracellular but not cell surface membrane IL-10Ralpha. Unresponsiveness of COX-2 to IL-10 is due to the deficiency of IL-10Ralpha on the surface of NSCLC cells. Our findings highlight a novel mechanism contributing to maintenance of elevated COX-2 and PGE(2) in the lung tumor environment.