Systemic treatment with neuropeptide Y receptor Y1-antagonist enhances atherosclerosis and stimulates IL-12 expression in ApoE deficient mice

Roles and Mechanisms of Interleukin-12 Family Members in Cardiovascular Diseases: Opportunities and Challenges

“…Elevated serum IL-12 levels are observed of atherosclerosis in ApoE-KO mice, and increased IL-12 levels are associated with the progression of atherosclerosis (Jääskeläinen et al, 2013). Accumulating animal study reports also demonstrate that treatment with exogenous recombinant murine IL-12 significantly aggravates the progression of atherosclerosis, and increases aortic atherosclerotic plaque areas in both ApoEknockout mice and in low density lipoprotein (LDL) receptordeficient mice, while cancelation the biological effects of IL-12 can significantly diminish such effects (Lee et al, 1999;Davenport and Tipping, 2003;Hauer et al, 2005).…”

“…Induce and promote th17 differentiation IL-27 alone has no apparent stimulatory properties, collaboration with other ILs promote or inhibit T cell differentiation and proliferation Promote Treg activity, suppress the Teff cell (Th1, and Th17 ) activity Ma and Trinchieri, 2001;Kastelein et al, 2007;Collison and Vignali, 2008;Vignali et al, 2008;Cox et al, 2011;Vignali and Kuchroo, 2012;Wojno and Hunter, 2012;Sun et al, 2015 Regulation of inflammation Except inflammatory environment induced by DOX or Ang II, all play pro-inflammatory role Always play a proinflammatory roles, no anti-inflammatory effects had been reported Not only play an anti-inflammatory role, but also play a proinflammatory effects, may be associated with inflammatory microenvironment Always relieves the inflammatory response Davenport and Tipping, 2003;Vignali and Kuchroo, 2012;Jin et al, 2012;Koltsova et al, 2012;Li et al, 2012;Yan et al, 2012;Jääskeläinen et al, 2013;Abbas et al, 2015;Subramanian et al, 2015;Sun et al, 2015;Andrews et al, 2016;Tao et al, 2016;Hu et al, 2016;Gregersen et al, 2017;Fatkhullina et al, 2018;Ye et al, 2018b;Jia et al, 2019;Liu et al, 2019;Vargas-Alarcón et al, 2019;Ye et al, 2019 family members have significantly higher levels of expression in patients with atherosclerosis and coronary artery disease, and are closely related to the progression of these diseases.…”

The potential role of IL-33/ST2 signaling in fibrotic diseases

“…Th1 and Th2 cells are both key regulators in this disease [91,92], and T regulatory cells act as important regulators of the Th1/Th2 balance [93]. Th1 cytokines, such as IL-12 [94,95], IL-18 [96], and IFN-g [96,97], have been shown to promote atherosclerosis, whereas Th2-related cytokines, such as IL-10 [98,99], IL-5 [100,101], and IL-13 [102], were demonstrated to have antiatherogenic effects. The first study linking IL-33 with atherosclerosis showed that IL-33 may play a protective role in the development of atherosclerosis via the induction of IL-5, which helps control the balance of Th1/Th2.…”

Heterogeneity of Tregs and the complexity in the IL-12 cytokine family signaling in driving T-cell immune responses in atherosclerotic vessels

“…This is supported by multiple experimental data showing association between circulating IL-12 levels and arterial stiffness (Yong et al, 2013), increased IL-12 production in apoE-deficient mice (Jääskeläinen et al, 2013;Wan et al, 2013) and diabetic patients with cardiovascular complications (Mishra et al, 2011), correlation between serum IL-12 concentrations and advanced inflammatory responses in murine models of atherosclerosis (Kleemann et al, 2008) and CAD patients (Ranjbaran et al, 2007), etc. IL-12 was found to induce from FoxP3+ Tregs IFN-␥-producing FoxP3+ T cells harboring immunosuppressive properties and capable to inhibit experimental colitis in mice.…”