title: GEC-derived SFRP5 inhibits Wnt5a-induced macrophage chemotaxis and activation.
abstract: Aberrant macrophage infiltration and activation has been implicated in gastric inflammation and carcinogenesis. Overexpression of Wnt5a and downregulation of SFRP5, a Wnt5a antagonist, were both observed in gastric cancers recently. This study attempted to explore whether Wnt5a/SFRP5 axis was involved in macrophage chemotaxis and activation. It was found that both Wnt5a transfection and recombinant Wnt5a (rWnt5a) treatment upregulated CCL2 expression in macrophages, involving JNK and NFκB signals. Conditioned medium from Wnt5a-treated macrophages promoted macrophage chemotaxis mainly dependent on CCL2. SFRP5 from gastric epithelial cells (GECs) inhibited Wnt5a-induced CCL2 expression and macrophage chemotaxis. In addition, Wnt5a treatment stimulated macrophages to produce inflammatory cytokines and COX-2/PGE2, which was also suppressed by SFRP5 from GECs. These results demonstrate that Wnt5a induces macrophage chemotaxis and activation, which can be blocked by GEC-derived SFRP5, suggesting that Wnt5a overproduction and SFRP5 deficiency in gastric mucosa may together play an important role in gastric inflammation and carcinogenesis.
authors.affiliation: Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, China.
authors.forename: Chenghai
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Xianmin
authors.initials: X
authors.lastname: Bu
authors.affiliation: Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, China.
authors.forename: Tingxian
authors.initials: T
authors.lastname: Ma
authors.affiliation: Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Ma
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects* / Q000235:genetics; D017077:Culture Media, Conditioned / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005136:Eye Proteins / Q000235:genetics / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D000071818:Wnt-5a Protein; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018932:Chemokine CCL2; D017077:Culture Media, Conditioned; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D005136:Eye Proteins; D048670:MAP Kinase Kinase 4; D008565:Membrane Proteins; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C111835:CCL2 protein, human; C118511:SFRP5 protein, human; D000094742:Secreted Frizzled-Related Proteins; C085389:WNT5A protein, human; C496540:PTGS2 protein, human