Interleukin-27 inhibits foam cell formation by promoting macrophage ABCA1 expression through JAK2/STAT3 pathway

Fu, Hui; Tang, Yue; Ouyang, Xin; Tang, Shilin; Su, Hua; Li, Xiaotao; Huang, Liping; He, Miao; Lv, Yun-Cheng; He, Ping; Yao, Feng; Tan, Yanhong; Xie, Wei; Zhang, Min; Wu, Jianfeng; Li, Yuan; Chen, Kong; Liu, Dan; Lan, Gang; Zeng, Meng-Ya; Zheng, Xi-Long; Tang, Chao-Ke

doi:10.1016/j.bbrc.2014.08.120

Cited by 27 publications

(21 citation statements)

References 32 publications

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“…In the present study, we mainly used THP-1 cells to detect the effect and mechanism of sCD40L on foam cell formation. Although many studies have used THP-1 cells as an in vitro cell model of macrophages to study foam cell formation [58,59,60], THP-1 cells are abnormal malignant monocytes. Their behaviors may not be completely the same as macrophages in vivo.…”

Section: Discussionmentioning

confidence: 99%

Soluble CD40 Ligand Promotes Macrophage Foam Cell Formation in the Etiology of Atherosclerosis

Yuan

Fu²,

Ren³

et al. 2015

Cardiology

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Objective: High levels of soluble CD40 ligand (sCD40L) in the circulation have been suggested as an important indicator of cardiovascular diseases such as atherosclerosis and acute coronary syndromes. In the present study, we explored the role of sCD40L in the formation of foam cells. Methods: Lipid deposition and foam cell formation was measured by high-performance liquid chromatography and Nile Red staining, respectively. Gene expressions were detected by quantitative real-time PCR and Western blot analysis. The interaction between CD40 and sCD40L were blocked by CD40 small interfering RNA or anti-CD40 antibody. Results: sCD40L significantly increased lipid deposition and foam cell formation associated with upregulation of scavenger receptor type A and CD36. Additionally, sCD40L increased adipocyte enhancer-binding protein 1 and cholesterol efflux, and activated NF-κB in macrophages. sCD40L promoted foam cell formation via CD40 ligation and disruption of the ligation between CD40 and CD40L either by small interfering RNA or by a blocking anti-CD40 antibody apparently inhibiting foam cell formation in response to sCD40L. Conclusion: Our data suggests a novel insight into the role of sCD40L in foam cell formation during atherosclerosis, which further confirms the importance of sCD40L in atherosclerosis and as a target for the treatment of this disease.

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Section: Discussionmentioning

confidence: 99%

Soluble CD40 Ligand Promotes Macrophage Foam Cell Formation in the Etiology of Atherosclerosis

Yuan

Fu²,

Ren³

et al. 2015

Cardiology

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“…IL-27 induces p-STAT3 to promote Th17 differentiation in the absence of STAT1 [16]. These Th17 regulators also exert their roles in T2DM and CAD, although relevant clinical studies are few [14, 17–19]. …”

Section: Introductionmentioning

confidence: 99%

Interleukin-22 Might Act as a Double-Edged Sword in Type 2 Diabetes and Coronary Artery Disease

Gong

Zhou

et al. 2016

Mediators of Inflammation

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Type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) are both characterized by chronic low-grade inflammation. The role of Th17 and its related cytokines in T2DM and CAD is unclear. Here we investigated the serum levels of five Th17-related cytokines (IL-17, IL-22, MIP-3α, IL-9, and IL-27) in T2DM, CAD, and T2DM-CAD comorbidity patients. IL-22 was found to be elevated in all three conditions. Elevated serum IL-22 was independently associated with the incidence of T2DM and CAD. Conversely, IL-22 was found to protect endothelial cells from glucose- and lysophosphatidylcholine- (LPC-) induced injury, and IL-22R1 expression on endothelial cells was increased upon treatment with high glucose and LPC. Blocking of IL-22R1 with IL-22R1 antibody diminished the protective role of IL-22. Our results suggest that IL-22 functions as a double-edged sword in T2DM and CAD and that IL-22 may be used in the treatment of chronic inflammatory diseases such as T2DM and CAD.

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“…In consistence with this finding, LDL-cholesterol suppresses MM cell apoptosis in culture [28] and blockade of the cholesterol transport by an anti-cancer agent JNJ-26854165 induces MM cell apoptosis [27]. If SC09 indeed inhibits cholesterol absorption, it will be of interest because the JAK2-STAT3 pathway is found to promote ABCA1 expression [29]. Therefore, it is possible that SC09 as an inhibitor of the JAK2-STAT3 inhibits cholesterol absorption by downregulating ABCA1 expression.…”

Section: Discussionmentioning

confidence: 99%

An inhibitor of cholesterol absorption displays anti-myeloma activity by targeting the JAK2-STAT3 signaling pathway

Han

Zhu

et al. 2016

Oncotarget

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The activated JAK2-STAT3 signaling pathway is a high risk factor for multiple myeloma (MM), a fatal malignancy of plasma cells. In the present study, SC09, a potential inhibitor of cholesterol absorption, was identified in a STAT3-targeted drug screen. SC09 suppressed the activation of STAT3 in a time-course and concentration-dependent manner but did not affect its family members STAT1 and STAT5. SC09 inhibited STAT3 transcriptional activity and downregulated the expression of STAT3-regulated genes. Further studies showed that SC09 selectively inhibited JAK2 activation but not other kinases including c-Src, ERK, p38 and mTOR that are all associated with STAT3 activation. Moreover, SC09 obviously induced MM cell death in vitro and delayed MM tumor growth in vivo. SC09-induced MM cell death was dependent on the endogenous STAT3 status, and this effect could be attenuated by enforced expression of STAT3. All the results collectively indicated that SC09 blocks the JAK2-STAT3 signaling thus displaying anti-MM activity. Given its well tolerance and anti-MM potency, SC09 is credited for further investigation as a promising drug for MM treatment.

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Interleukin-27 inhibits foam cell formation by promoting macrophage ABCA1 expression through JAK2/STAT3 pathway

Cited by 27 publications

References 32 publications

Soluble CD40 Ligand Promotes Macrophage Foam Cell Formation in the Etiology of Atherosclerosis

Soluble CD40 Ligand Promotes Macrophage Foam Cell Formation in the Etiology of Atherosclerosis

Interleukin-22 Might Act as a Double-Edged Sword in Type 2 Diabetes and Coronary Artery Disease

An inhibitor of cholesterol absorption displays anti-myeloma activity by targeting the JAK2-STAT3 signaling pathway

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