%0 Journal Article
%T Involvement of interleukin-1β in high glucose-activated proliferation of cholangiocarcinoma.
%A Khawkhiaw K
%A Chomphoo S
%A Kunprom W
%A Thithuan K
%A Sorin S
%A Yueangchantuek P
%A Chiu CF
%A Umezawa K
%A Panaampon J
%A Okada S
%A Wongkham S
%A Saengboonmee C
%J Transl Gastroenterol Hepatol
%V 9
%N 0
%D 2024
%M 39091665
暂无%R 10.21037/tgh-24-8
%X <B>UNASSIGNED: </B>Diabetes mellitus (DM) is associated with the increased risk of development and the advancement of cholangiocarcinoma (CCA). High glucose levels were previously shown for upregulating interleukin-1β (IL-1β) in CCA cells with unclear functions. The present study, thus, aimed to investigate molecular mechanisms linking DM to CCA progression, with IL-1β hypothesized as a communicating cytokine.<BR><B>UNASSIGNED: </B>CCA cells were cultured in media with normal (5.6 mM) or high (25 mM) glucose, resembling euglycemia and hyperglycemia, respectively. Expressions of IL-1β and IL-1 receptor (IL-1R) in CCA tissues from patients with and without DM were examined using immunohistochemistry. Functional analyses of IL-1β were performed using siRNA and recombinant human IL-1R antagonist (rhIL-1RA), in which Western blots investigated the knockdown efficacy. BALB/c Rag-2-/- Jak3-/- (BRJ) mice were implanted with CCA xenografts to investigate hyperglycemia's effects on CCA growth and the anti-tumor effects of IL-1RA.<BR><B>UNASSIGNED: </B>CCA tumors from patients with hyperglycemia showed significantly higher IL-1β expression than those from non-DM patients, while IL-1β was positively correlated with fasting blood glucose (FBG) levels. CCA cells cultured in high glucose showed increased IL-1β expression, resulting in increased proliferation rates. Suppressing IL-1β signaling by si-IL-1β or rhIL-1RA significantly reduced CCA cell proliferation in vitro. Anakinra, a synthetic IL-1RA, also exerted significant anti-tumor effects in vivo and significantly reversed the effects of hyperglycemia-induced growth in CCA xenografts.<BR><B>UNASSIGNED: </B>IL-1β plays a crucial role in CCA progression in a high-glucose environment. Targeting IL-1β might, then, help improve therapeutic outcomes of CCA in patients with DM and hyperglycemia.