PMID- 25963277 OWN - NLM STAT- MEDLINE DCOM- 20160229 LR - 20171116 IS - 1873-5169 (Electronic) IS - 0196-9781 (Linking) VI - 69 DP - 2015 Jul TI - Effects of Apelin on RAW264.7 cells under both normal and hypoxic conditions. PG - 133-43 LID - S0196-9781(15)00144-8 [pii] LID - 10.1016/j.peptides.2015.04.025 [doi] AB - Macrophages are an important source of pro-inflammatory and pro-angiogenic factors, which can promote pathological processes involving inflammation and angiogenesis. This study investigated the effects of Apelin on macrophages under both normal and hypoxic conditions. Under normal culture conditions, Apelin down-regulated the mRNA expression levels of monocyte chemotactic protein 1 (MCP1), monocyte chemotactic protein 3 (MCP3), macrophage inflammatory protein 1 (MIP1alpha, MIP1beta), vascular endothelial growth factor A (VEGFA), Angiopoietin 2 (Ang2) and tumor necrosis factor alpha (TNFalpha). The supernatant concentrations of MCP1, MCP3, MIP1alpha, MIP1beta, macrophage inflammatory protein 2 (MIP2) and TNFalpha proteins were significantly decreased in the Apelin treated group. Hypoxia induced profound up-regulations of the angiogenic, chemokine, and inflammatory factors at both the mRNA and protein levels. Apelin suppressed the hypoxia-induced increases in MCP1, MCP3, MIP2, MIP1beta and TNFalpha expression. The underlying mechanism of Apelin inhibit inflammation is regulating NF-kappaB/JNK signal pathway. Additionally, Apelin can protect macrophages from apoptosis and can enhance cell migration during hypoxia. And cleaved Caspase9/3 pathways were involved in Apelin inhibiting RAW264.7 apoptosis. In conclusion, we showed the effect of Apelin on RAW264.7 macrophage under normal and hypoxic condition, which could further influence the angiogenesis and inflammation process that promoted by macrophages. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Yang, Fan AU - Yang F AD - Department of Ophthalmology, Peking University People's Hospital, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing Key Laboratory for the Diagnosis and Treatment of Retinal and Choroid Diseases, Beijing, China. FAU - Bai, Yujing AU - Bai Y AD - Department of Ophthalmology, Peking University People's Hospital, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing Key Laboratory for the Diagnosis and Treatment of Retinal and Choroid Diseases, Beijing, China. Electronic address: baiyujing93@gmail.com. FAU - Jiang, Yanrong AU - Jiang Y AD - Department of Ophthalmology, Peking University People's Hospital, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing Key Laboratory for the Diagnosis and Treatment of Retinal and Choroid Diseases, Beijing, China. Electronic address: drjiangyr@gmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150509 PL - United States TA - Peptides JT - Peptides JID - 8008690 RN - 0 (Adipokines) RN - 0 (Angiopoietin-2) RN - 0 (Apelin) RN - 0 (Apln protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CCL4) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Peptides) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (vascular endothelial growth factor A, mouse) SB - IM MH - Adipokines/administration & dosage/genetics/*metabolism MH - Angiopoietin-2/biosynthesis MH - Animals MH - Apelin MH - Cell Movement/genetics MH - Chemokine CCL2/biosynthesis/genetics MH - Chemokine CCL4/biosynthesis/genetics MH - Gene Expression Regulation/drug effects MH - Inflammation/genetics/*metabolism/pathology MH - Intercellular Signaling Peptides and Proteins/administration & dosage/genetics/*metabolism MH - Macrophages/drug effects/*metabolism/pathology MH - Mice MH - Neovascularization, Pathologic/genetics/metabolism MH - Peptides/administration & dosage/chemical synthesis/*metabolism MH - Tumor Necrosis Factor-alpha/biosynthesis MH - Vascular Endothelial Growth Factor A/biosynthesis OTO - NOTNLM OT - Angiogenesis OT - Apelin OT - Hypoxia OT - Inflammation OT - Macrophage EDAT- 2015/05/13 06:00 MHDA- 2016/03/02 06:00 CRDT- 2015/05/13 06:00 PHST- 2014/12/10 00:00 [received] PHST- 2015/04/22 00:00 [revised] PHST- 2015/04/29 00:00 [accepted] PHST- 2015/05/13 06:00 [entrez] PHST- 2015/05/13 06:00 [pubmed] PHST- 2016/03/02 06:00 [medline] AID - S0196-9781(15)00144-8 [pii] AID - 10.1016/j.peptides.2015.04.025 [doi] PST - ppublish SO - Peptides. 2015 Jul;69:133-43. doi: 10.1016/j.peptides.2015.04.025. Epub 2015 May 9.