Interleukin-18-mediated interferon-gamma secretion is regulated by thymosin beta 4 in human NK cells

Abstract

Thymosin beta 4 (T beta 4) is the major G-actin sequestering molecule and is abundant in lymphoid tissues. However, it is not clear what regulates T beta 4 expression and what its function is on natural killer (NK) cells. We investigated whether interleukin-18 (IL-18) has a role in T beta 4 expression and if enhanced T beta 4 influences IL-18-mediated interferon-gamma (IFN-gamma) secretion. In this study, recombinant human IL-18 (rhIL-18) enhanced the endogenous level of T beta 4 through p38MAPK and JNK signaling pathway in the human NK cell line, NK-92MI. Overexpression of endogeneous T beta 4 stimulated IFN-gamma expression and secretion. Additionally, pretreatment with an inhibitor for T beta 4 decreased IL-18-enhanced IFN-gamma secretion, and transfection with T beta 4-specific short hairpin RNA resulted in reduction of IFN-gamma production in primary NK cells as well as in the human NK cell line. Taken together, these data indicated that T beta 4 is regulated by IL-18 and is involved in IL-18-enhanced IFN-gamma secretion in NK cells. (c) 2011 Elsevier GmbH. All rights reserved.