Leptin enhances CC-chemokine ligand expression in cultured murine macrophage.
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.
Kiguchi
Norikazu
N
Department of Pharmacology, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Wakayama 641-0012, Japan.
Maeda
Takehiko
T
Kobayashi
Yuka
Y
Fukazawa
Yohji
Y
Kishioka
Shiroh
S
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
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