title: 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.
authors.affiliation: Division of Pediatric Endocrinology, Children's Hospital of Philadelphia, Pennsylvania, United States of America.
authors.forename: Rachana D
authors.initials: RD
authors.lastname: Shah
authors.affiliation: Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.|Department of Medicine, Columbia University, New York, New York, United States of America.
authors.forename: Chenyi
authors.initials: C
authors.lastname: Xue
authors.affiliation: Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.|Department of Medicine, Columbia University, New York, New York, United States of America.
authors.forename: Hanrui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Sony
authors.initials: S
authors.lastname: Tuteja
authors.affiliation: Department of Biostatistics & Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.|Department of Medicine, Columbia University, New York, New York, United States of America.
authors.forename: Muredach P
authors.initials: MP
authors.lastname: Reilly
authors.affiliation: Division of Cardiovascular Medicine, and Vanderbilt Translational and Clinical Cardiovascular Research Center (VTRACC), Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Jane F
authors.identifier: http://orcid.org/0000-0001-6896-1025
authors.initials: JF
authors.lastname: Ferguson
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage*; D002081:Buttocks; D040501:Calgranulin A / Q000235:genetics* / Q000378:metabolism; D040502:Calgranulin B / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage*; D019446:Endotoxemia / Q000139:chemically induced / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D005786:Gene Expression Regulation; D064368:Healthy Volunteers; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000067616:S100A12 Protein / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000975:Antioxidants; D040501:Calgranulin A; D040502:Calgranulin B; D008070:Lipopolysaccharides; D000067616:S100A12 Protein; C090441:S100A12 protein, human; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid