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Interleukin-18-mediated interferon-gamma secretion is regulated by thymosin beta 4 in human NK cells
Authors:Lee Ha-reum  Yoon Sun Young  Song Seok Bean  Park Yoorim  Kim Tae Sung  Kim Seonghan  Hur Dae Young  Song Hyun Keun  Park Hyunjeong  Cho Daeho
Affiliation:a Department of Life Science, Sookmyung Women's University, Seoul, Republic of Korea
b School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea
c Department of Anatomy, Inje University College of Medicine, Pusan, Republic of Korea
d Department of Dermatology, St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
Abstract:Thymosin beta 4 (Tβ4) is the major G-actin sequestering molecule and is abundant in lymphoid tissues. However, it is not clear what regulates Tβ4 expression and what its function is on natural killer (NK) cells. We investigated whether interleukin-18 (IL-18) has a role in Tβ4 expression and if enhanced Tβ4 influences IL-18-mediated interferon-gamma (IFN-γ) secretion. In this study, recombinant human IL-18 (rhIL-18) enhanced the endogenous level of Tβ4 through p38MAPK and JNK signaling pathway in the human NK cell line, NK-92MI. Overexpression of endogeneous Tβ4 stimulated IFN-γ expression and secretion. Additionally, pretreatment with an inhibitor for Tβ4 decreased IL-18-enhanced IFN-γ secretion, and transfection with Tβ4-specific short hairpin RNA resulted in reduction of IFN-γ production in primary NK cells as well as in the human NK cell line. Taken together, these data indicated that Tβ4 is regulated by IL-18 and is involved in IL-18-enhanced IFN-γ secretion in NK cells.
Keywords:Interleukin-18   Natural killer cells   Thymosin beta 4   Interferon-gamma
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