title: Leptin enhances CC-chemokine ligand expression in cultured murine macrophage.
abstract: Despite accumulating evidence, the role of leptin in chemokine expression is poorly understood. In this study, we evaluated the effects of leptin on CC-chemokine ligands (CCLs), CCL3, CCL4, and CCL5 gene expression in cultured murine macrophage, J774A.1 cells. Expression of all these CCLs mRNA was gradually increased and significant up-regulation was observed for 3-12 h exposure to leptin (1 microM). The phosphorylated signal transducer and activator of transcription 3 (pSTAT3) was significantly increased for 5-20 min exposure to leptin, and it was localized in leptin receptor-positive macrophage. Pretreatment with AG490 (100 microM), a janus kinase 2 (JAK2) inhibitor, significantly suppressed leptin-induced pSTAT3 increases and the up-regulation of CCLs mRNA expression. In conclusion, leptin enhances CCLs expression in cultured murine macrophage, through activation of a JAK2-STAT3 pathway. Therefore, a new paradigm of leptin-mediated chemokine expression may lead to the clarification of complex immune systems in future.
authors.affiliation: Department of Pharmacology, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Wakayama 641-0012, Japan.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Kiguchi
authors.forename: Takehiko
authors.initials: T
authors.lastname: Maeda
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Yohji
authors.initials: Y
authors.lastname: Fukazawa
authors.forename: Shiroh
authors.initials: S
authors.lastname: Kishioka
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D054405:Chemokine CCL3 / Q000235:genetics*; D054407:Chemokine CCL4 / Q000235:genetics*; D018946:Chemokine CCL5 / Q000235:genetics*; D019742:Chemokines, CC / Q000276:immunology*; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation; D053614:Janus Kinase 2 / Q000378:metabolism; D020738:Leptin / Q000494:pharmacology / Q000502:physiology*; D008024:Ligands; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: C496534:Ccl3 protein, mouse; C503460:Ccl5 protein, mouse; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC; D020738:Leptin; D008024:Ligands; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D053614:Janus Kinase 2