title: Fatty acid-binding protein 5 limits the anti-inflammatory response in murine macrophages.
abstract: The beginning stages of liver damage induced by various etiologies (i.e. high fat diet, alcohol consumption, toxin exposure) are characterized by abnormal accumulation of lipid in liver. Alterations in intracellular lipid transport, storage, and metabolism accompanied by cellular insult within the liver play an important role in the pathogenesis of liver disease, often involving a sustained inflammatory response. The intracellular lipid transporter, fatty acid binding protein 5 (FABP5), is highly expressed in macrophages and may play an important role in the hepatic inflammatory response after endotoxin exposure in mice. This study tested the hypothesis that FABP5 regulates macrophage response to LPS in male C57bl/6 (wild type) and FABP5 knockout mice, both in vitro and in vivo. Treatment with LPS revealed that loss of FABP5 enhances the number of hepatic F4/80(+) macrophages in the liver despite limited liver injury. Conversely, FABP5 knock out mice display higher mRNA levels of anti-inflammatory cytokines IL-10, arginase, YM-1, and Fizz-1 in liver compared to wild type mice. Bone marrow derived macrophages stimulated with inflammatory (LPS and IFN-γ) or anti-inflammatory (IL-4) mediators also showed significantly higher expression of anti-inflammatory/regulatory factors. These findings reveal a regulatory role of FABP5 in the acute inflammatory response to LPS-induced liver injury, which is consistent with the principle finding that FABP5 is a regulator of macrophage phenotype. Specifically, these findings demonstrate that loss of FABP5 promotes a more anti-inflammatory response.
authors.affiliation: Department of Nutrition Science, College of Human Ecology, East Carolina University, Greenville, NC 27858, United States. Electronic address: Mooresh06@students.ecu.edu.
authors.forename: Sherri M
authors.initials: SM
authors.lastname: Moore
authors.affiliation: Department of Nutrition Science, College of Human Ecology, East Carolina University, Greenville, NC 27858, United States. Electronic address: Holtv14@students.ecu.edu.
authors.forename: Vivian V
authors.initials: VV
authors.lastname: Holt
authors.affiliation: Department of Nutrition Science, College of Human Ecology, East Carolina University, Greenville, NC 27858, United States. Electronic address: Malpassl14@students.ecu.edu.
authors.forename: Lillie R
authors.initials: LR
authors.lastname: Malpass
authors.affiliation: Department of Nutrition Science, College of Human Ecology, East Carolina University, Greenville, NC 27858, United States. Electronic address: Hines1@ecu.edu.
authors.forename: Ian N
authors.initials: IN
authors.lastname: Hines
authors.affiliation: Department of Nutrition Science, College of Human Ecology, East Carolina University, Greenville, NC 27858, United States. Electronic address: Wheelerm@ecu.edu.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Wheeler
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D016764:Cell Polarity / Q000187:drug effects; D002469:Cell Separation; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000293:injuries / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D020556:Neutrophil Infiltration / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; C082667:Fabp5 protein, mouse; D050556:Fatty Acid-Binding Proteins; D008070:Lipopolysaccharides; D009363:Neoplasm Proteins; D012333:RNA, Messenger
keywords: Anti-inflammatory macrophage (M2); Fatty acid binding protein-5 (FABP(5)); Macrophage polarization; Pro-inflammatory macrophage (M1)