Cross Talk Between Vascular Smooth Muscle Cells and Monocytes Through Interleukin-1β/Interleukin-18 Signaling Promotes Vein Graft Thickening
Year: 2014
Type: article
Abstract: OBJECTIVE: Interleukin (IL)-1β and IL-18 are key proinflammatory cytokines that play important roles in the pathophysiology of vein graft remodeling. However, the mechanism of IL-1β/IL-18 production and its role in the development of graft remodeling remain unclear. APPROACH AND RESULTS: IL-1β/IL-18 were rapidly expressed in venous interposition grafts. Vascular smooth muscle cell (VSMC) death and monocytic inflammasome activation occurred in grafted veins. Necrotic VSMCs induced the expression of IL-1β, IL-18, and other inflammasome-associated proteins in monocytes, which was partially inhibited by their antagonist, recombinant IL-1ra-Fc-IL-18bp. Activated monocytes stimulated proliferation of VSMCs by activating cell growth-related signaling molecules (AKT, STAT3, ERK1/2, and mTOR [AKT/protein kinase B, signal transducer and activator of transcription 3, extracellular signal-regulated kinase 1/2, mammalian target of rapamycin]) and increasing production of platelet-derived growth factor-bb; these effects were suppressed by IL-1ra-Fc-IL-18bp. Activated monocytes also promoted migration of VSMCs, which was independent of IL-1β/IL-18 signaling. Importantly, administration of IL-1ra-Fc-IL-18bp inhibited activation of cell growth-related signaling molecules, VSMC proliferation, and vein graft thickening in vivo. CONCLUSIONS: Our work identified an interaction among necrotic VSMCs, monocytes, and viable VSMCs through IL-1β/IL-18 signaling, which might be exploited as a therapeutic target in vein graft remodeling.
Authors: Ping Li, Yu-lin Li, Zhen-ya Li, Yi-na Wu, Cong-cong Zhang, Xi A, Chun-xiao Wang, Hong-tao Shi, Mi-zhou Hui, Bo Xie, Mohammed Ahmed, Jie Du
Institutions: Baylor College of Medicine, Capital Medical University, Chinese Academy of Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Anzhen Hospital, Institute of Process Engineering, Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2159886553