Expression of Calgranulin Genes S100A8, S100A9 and S100A12 Is Modulated by n-3 PUFA during Inflammation in Adipose Tissue and Mononuclear Cells

Abstract

Calgranulin genes (S100A8, S100A9 and S100A12) play key immune response roles in inflammatory disorders, including cardiovascular disease. Long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) may have systemic and adipose tissue-specific anti-inflammatory and cardio-protective action. Interactions between calgranulins and the unsaturated fatty acid arachidonic acid (AA) have been reported, yet little is known about the relationship between calgranulins and the LC n-3 PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We explored tissue-specific action of calgranulins in the setting of evoked endotoxemia and n-3 PUFA supplementation. Expression of calgranulins in adipose tissue in vivo was assessed by RNA sequencing (RNASeq) before and after n-3 PUFA supplementation and evoked endotoxemia in the fenofibrate and omega-3 fatty acid modulation of endotoxemia (FFAME) Study. Subjects received n-3 PUFA (n = 8; 3600mg/day EPA/DHA) or matched placebo (n = 6) for 6–8 weeks, before completing an endotoxin challenge (LPS 0.6 ng/kg). Calgranulin genes were up-regulated post-LPS, with greater increase in n-3 PUFA (S100A8 15-fold, p = 0.003; S100A9 7-fold, p = 0.003; S100A12 28-fold, p = 0.01) compared to placebo (S100A8 2-fold, p = 0.01; S100A9 1.4-fold, p = 0.4; S100A12 5-fold, p = 0.06). In an independent evoked endotoxemia study, calgranulin gene expression correlated with the systemic inflammatory response. Through in vivo and in vitro interrogation we highlight differential responses in adipocytes and mononuclear cells during inflammation, with n-3 PUFA leading to increased calgranulin expression in adipose, but decreased expression in circulating cells. In conclusion, we present a novel relationship between n-3 PUFA anti-inflammatory action in vivo and cell-specific modulation of calgranulin expression during innate immune activation.

Body Mass Index and Calprotectin Blood Level Correlation in Healthy Children: An Individual Patient Data Meta-Analysis

“…On the other hand, the link between CP levels and BMI z-score shows substantial dispersion, from which we infer that many other factors modulate the intensity of subclinical inflammation. For example, polyunsaturated fatty acids exert different tissue-dependent effects on CP levels [21]. Unlike a previous report [6], we did not find sex to be a significant modulator of CP levels, although a trend was potentially present.…”

S100A12 Expression Is Modulated During Monocyte Differentiation and Reflects Periodontitis Severity

“…In agreement with our findings, Sander et al (32) have shown that monocytes differentiated by CSF-1 had lower expression of S100A12 in comparison with CD14 + monocytes. Similarly, Shah et al (11) have found decreased expression of S100A12 during maturation of monocytes to macrophages along with unaltered expression following polarization. Thus, S100A12 is part of the genes that are rapidly regulated during differentiation, maintained in mature macrophages, and refractory to polarization (31).…”

“…S100A12 is mainly expressed in the cytoplasm of myeloid cells and, upon release, acts as a proinflammatory alarmin (9,10). Interestingly, its gene expression is higher in classical than in non-classical monocytes (3,6), and it decreases during monocyte to macrophage maturation (11). S100A12 binds to receptor for advanced glycation end products (RAGE) and TLR4, it is chemotactic for leukocytes and induces a strong inflammatory response in monocytes (12,13).…”

Dietary fatty acids and adipose tissue inflammation at the crossroad between obesity and colorectal cancer

“…Additionally, consumption of different sources of fatty fish reduces the expression of AT inflammatory genes including inflammasomeassociated IL-18, IL-1β and IL1RN or impairs fasting glucose in obese subjects [43,51] . Moreover, in a clinical trial (FFAME) involving healthy volunteers and based on eicosapentaenoic and decosahexaenoic acid supplementation, ω3 PUFA showed immune-modulatory and anti-inflammatory capability through the modulation of several inflammatory and specific immune genes during evoked AT inflammation induced by experimental endotoxemia [52,53] . In contrast to these results, no effect on SAT inflammation was observed neither in overweight to moderately obese adults consuming a diet rich in ω3 PUFA [54] , nor in obese postmenopausal women after decosahexaenoic acid supplementation [55] .…”