scholarly journals Interleukin-6 induces hepcidin expression through STAT3

Blood ◽  
2006 ◽  
Vol 108 (9) ◽  
pp. 3204-3209 ◽  
Author(s):  
Diedra M. Wrighting ◽  
Nancy C. Andrews
Keyword(s):  
Iron Deficiency ◽  
Interleukin 6 ◽  
Inflammatory Cytokine ◽  
Iron Homeostasis ◽  
Signal Transducer ◽  
Hepcidin Expression ◽  
Inflammatory Stimuli ◽  
High Result ◽  
Necessary And Sufficient ◽  
Transcription 3

Abstract Iron homeostasis is maintained through meticulous regulation of circulating hepcidin levels. Hepcidin levels that are inappropriately low or high result in iron overload or iron deficiency, respectively. Although hypoxia, erythroid demand, iron, and inflammation are all known to influence hepcidin expression, the mechanisms responsible are not well defined. In this report we show that the inflammatory cytokine interleukin-6 (IL-6) directly regulates hepcidin through induction and subsequent promoter binding of signal transducer and activator of transcription 3 (STAT3). STAT3 is necessary and sufficient for the IL-6 responsiveness of the hepcidin promoter. Our findings provide a mechanism by which hepcidin can be regulated by inflammation or, in the absence of inflammatory stimuli, by alternative mechanisms leading to STAT3 activation.

scholarly journals Macrophage-derived interleukin-6 is necessary and sufficient for choroidal angiogenesis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Steven Droho ◽  
Carla M. Cuda ◽  
Harris Perlman ◽  
Jeremy A. Lavine
Keyword(s):  
Interleukin 6 ◽  
Vision Loss ◽  
Age Related Macular Degeneration ◽  
Signal Transducer ◽  
Treatment Resistant ◽  
Sprouting Angiogenesis ◽  
Laser Injury ◽  
Age Related ◽  
Necessary And Sufficient ◽  
Transcription 3

AbstractNeovascular age-related macular degeneration (nAMD) commonly causes vision loss from aberrant angiogenesis, termed choroidal neovascularization (CNV). Interleukin-6 (IL6) is a pro-inflammatory and pro-angiogenic cytokine that is correlated with AMD progression and nAMD activity. We hypothesize that anti-IL6 therapy is a potential nAMD therapeutic. We found that IL6 levels were increased after laser injury and expressed by macrophages. Il6-deficiency decreased laser-induced CNV area and exogenous IL6 addition increased choroidal sprouting angiogenesis. Il6-null mice demonstrated equally increased macrophage numbers as wildtype mice. At steady state, IL6R expression was detected on peripheral blood and ocular monocytes. After laser injury, the number of IL6R+Ly6C+ monocytes in blood and IL6R+ macrophages in the eye were increased. In human choroid, macrophages expressed IL6, IL6R, and IL6ST. Furthermore, IL6R+ macrophages displayed a transcriptional profile consistent with STAT3 (signal transducer and activator of transcription 3) activation and angiogenesis. Our data show that IL6 is both necessary and sufficient for choroidal angiogenesis. Macrophage-derived IL6 may stimulate choroidal angiogenesis via classical activation of IL6R+ macrophages, which then stimulate angiogenesis. Targeting IL6 or the IL6R could be an effective adjunctive therapy for treatment-resistant nAMD patients.

scholarly journals Cholestasis downregulate hepcidin expression through inhibiting IL-6-induced phosphorylation of signal transducer and activator of transcription 3 signaling

2009 ◽  
Vol 89 (10) ◽  
pp. 1128-1139 ◽  
Author(s):  
Ying-Hsien Huang ◽  
Jiin-Haur Chuang ◽  
Ya-Ling Yang ◽  
Chao-Cheng Huang ◽  
Chia-Ling Wu ◽  
...  
Keyword(s):  
Signal Transducer ◽  
Hepcidin Expression ◽  
Transcription 3

Hepcidin as a Prospective Individualized Biomarker for Individuals at Risk of Low Energy Availability

2019 ◽  
Vol 29 (6) ◽  
pp. 671-681 ◽  
Author(s):  
Claire E. Badenhorst ◽  
Katherine E. Black ◽  
Wendy J. O’Brien
Keyword(s):  
Iron Deficiency ◽  
Iron Homeostasis ◽  
Dietary Intervention ◽  
Low Energy ◽  
Energy Availability ◽  
Dietary Interventions ◽  
Hepcidin Expression ◽  
Ketogenic Diets ◽  
Increased Risk ◽  
Low Energy Availability

Hepcidin, a peptide hormone with an acknowledged evolutionary function in iron homeostasis, was discovered at the turn of the 21st century. Since then, the implications of increased hepcidin activity have been investigated as a potential advocate for the increased risk of iron deficiency in various health settings. Such implications are particularly relevant in the sporting community where peaks in hepcidin postexercise (∼3–6 hr) are suggested to reduce iron absorption and recycling, and contribute to the development of exercise-induced iron deficiency in athletes. Over the last decade, hepcidin research in sport has focused on acute and chronic hepcidin activity following single and repeated training blocks. This research has led to investigations examining possible methods to attenuate postexercise hepcidin expression through dietary interventions. The majority of macronutrient dietary interventions have focused on manipulating the carbohydrate content of the diet in an attempt to determine the health of athletes adopting the low-carbohydrate or ketogenic diets, a practice that is a growing trend among endurance athletes. During the process of these macronutrient dietary intervention studies, an observable coincidence of increased cumulative hepcidin activity to low energy availability has emerged. Therefore, this review aims to summarize the existing literature on nutritional interventions on hepcidin activity, thus, highlighting the link of hepcidin to energy availability, while also making a case for the use of hepcidin as an individualized biomarker for low energy availability in males and females.

Sign in / Sign up

Export Citation Format

Share Document