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CCL18/PARC increases pro‐inflammatory cytokines and cell survival in cultured monocytes
Author(s) -
Schraufstatter Ingrid U.,
Zhao Ming,
Khaldoyanidi Sophia,
Discipio Richard G
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a202-b
Subject(s) - ccl18 , chemokine , monocyte , cytokine , interleukin 8 , microbiology and biotechnology , ccl2 , tumor necrosis factor alpha , chemistry , biology , immune system , immunology
CCL18/PARC is a chemokine, which is a chemotactic factor for lymphocytes, immature dendritic cells and for cultured, but not freshly isolated monocytes. Three day old monocytes cultured in the presence of 40 nM CCL18 showed increased survival on day 4 (40–45% surviving cells compared to 15–25% in unstimulated controls). This observation led us to determine differences in gene and cytokine expression in CCL18‐stimulated versus control cultures. On the protein level CCL18 caused increased concentrations of IL‐6, IL‐8, gro‐α, ENA‐78, MCP‐1 and MIP‐1α, but down‐regulated angiogenin, bFGF and insulin‐like growth factor. Interestingly, two inhibitors of membrane metalloproteases (TIMP‐1 and TIMP‐2) were also down‐regulated following CCL18 stimulation. In addition, there was more MMP‐9 protein and activity detected in supernatants from CCL18‐activated monocytes.. Differential gene expression, which was detected by gene array was verified for several relevant genes by RT‐PCR. These genes included IL‐15 and stem cell factor, which were both up‐regulated and caspase 8, which was down‐regulated by CCL18.. In addition, IL‐15, ‐ which was shown by FACS to be up‐regulated on the cell surface of CCL18‐stimulated monocytes, ‐ has an anti‐apoptotic function in various leukocytes. Thus CCL18 induces pro‐inflammatory effects 1) directly by reducing monocyte apoptosis, 2) indirectly through increased production of cytokines/chemokines, which cause leukocyte influx, and 3) by contributing to connective tissue breakdown due to increased metalloprotease activity.