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Inflammatory cytokines stimulate the chemokines CCL2/MCP-1 and CCL7/MCP-7 through NFκB and MAPK dependent pathways in rat astrocytes
- Source :
-
Brain Research . Sep2009, Vol. 1287, p47-57. 11p. - Publication Year :
- 2009
-
Abstract
- Abstract: The chemokines CCL2 and CCL7 are upregulated in the brain during several neurodegenerative and acute diseases associated with infiltration of peripheral leukocytes. Astrocytes can respond to inflammatory cytokines like IL-1β and TNF-α by producing chemokines. This study aims to test the ability of IL-1β and TNF-α to stimulate CCL2 and CCL7 protein production in rat astrocyte cultures, and to elucidate signaling pathways involved in the cytokine-stimulated chemokine upregulation. Astrocytes were stimulated with IL-1β or TNF-α, and CCL2 and CCL7 levels determined by ELISA. Our results show that IL-1β and TNF-α each stimulate production of the chemokines CCL2 and CCL7 in astrocytes in a concentration- and time-dependent manner, with CCL2 showing a more rapid and robust response to the cytokine treatment than CCL7. As a first step to determine the signaling pathways involved in CCL2 and CCL7 upregulation, we stimulated astrocytes with IL-1β or TNF-α in the presence of selective inhibitors of MAPK pathways (SB203580 and SB202190 for p38, SP600125 for JNK, and U0126 for ERK) or NFκB pathways (MG-132 and SC-514). We found that NFκB pathways are important for the cytokine-stimulated CCL2 and CCL7 production, whereas MAPK pathways involving p38 and JNK, but not ERK, may also contribute but to a lesser extent. These data document for the first time that CCL7 protein production can be stimulated in astrocytes by cytokines, and that the upregulation may involve NFκB- and p38/JNK-regulated pathways. In addition, our results suggest that CCL2 and CCL7 share similarities in the signaling pathways necessary for their upregulation. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 00068993
- Volume :
- 1287
- Database :
- Academic Search Index
- Journal :
- Brain Research
- Publication Type :
- Academic Journal
- Accession number :
- 43666534
- Full Text :
- https://doi.org/10.1016/j.brainres.2009.06.081