PMID- 16408113 OWN - NLM STAT- MEDLINE DCOM- 20060223 LR - 20220318 IS - 0085-2538 (Print) IS - 0085-2538 (Linking) VI - 69 IP - 2 DP - 2006 Jan TI - Lipoxin A4 inhibits connective tissue growth factor-induced production of chemokines in rat mesangial cells. PG - 248-56 AB - Connective tissue growth factor (CTGF) is involved in mitogenesis, matrix production, and chemotaxis in mesenchymal cells. The effects of CTGF on the production of chemokines remain unclear. The present studies investigate the regulatory role of CTGF in the production of fractalkine, monocyte chemoattractant protein-1 (MCP-1), and RANTES (regulated upon activation, normal T cell expressed and secreted) in cultured mesangial cells of rats, and the modulatory effects of lipoxin A(4) (LXA(4)) on actions of CTGF. CTGF enhanced the mRNA expression and protein release of fractalkine, MCP-1, and RANTES, the expression of phospho (P)-p42/44 mitogen-activated protein kinase (MAPK), P-phosphoinositide 3-kinase (PI3-K), P-Akt, and activity of nuclear factor-kappaB (NF-kappaB) in mesangial cells. P-p42/44 MAPK blockade inhibited the CTGF-induced expression of P-p42/44 MAPK but not NF-kappaB, and partially decreased the levels of the above chemokines in supernatants. P-PI3-K blockade downregulated the CTGF-stimulated expression of P-PI3-K, P-Akt, and NF-kappaB but not P-p42/44 MAPK, and partially decreased the release of the above chemokines. NF-kappaB blockade abrogated the CTGF-activated NF-kappaB and partially decreased the secretion of the above chemokines. LXA(4) dose-dependently inhibited the CTGF-stimulated mRNA expression and protein release of the above chemokines, and the expression of P-p42/44MAPK, P-PI3-K, P-Akt, and NF-kappaB. In conclusion, these results demonstrate that CTGF induces production of fractalkine, MCP-1, and RANTES via the p42/44 MAPK-, PI3-K/Akt-, and NF-kappaB-dependent signal pathway, and LXA(4) downregulates the above effects of CTGF on rat mesangial cells. FAU - Wu, S-H AU - Wu SH AD - Department of Pediatrics, Central Laboratory, The First Affiliated Hospital of Nanjing Medical University, Jiangsu, People's Republic of China. kad-yc@163.com FAU - Wu, X-H AU - Wu XH FAU - Lu, C AU - Lu C FAU - Dong, L AU - Dong L FAU - Zhou, G-P AU - Zhou GP FAU - Chen, Z-Q AU - Chen ZQ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Kidney Int JT - Kidney international JID - 0323470 RN - 0 (CCN2 protein, rat) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CCL5) RN - 0 (Chemokine CX3CL1) RN - 0 (Chemokines) RN - 0 (Chemokines, CX3C) RN - 0 (Cx3cl1 protein, rat) RN - 0 (Immediate-Early Proteins) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Lipoxins) RN - 0 (Membrane Proteins) RN - 0 (NF-kappa B) RN - 0 (RNA, Messenger) RN - 0 (lipoxin A4) RN - 139568-91-5 (Connective Tissue Growth Factor) RN - 9007-49-2 (DNA) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Animals MH - Cell Movement MH - Cells, Cultured MH - Chemokine CCL2/biosynthesis MH - Chemokine CCL5/biosynthesis MH - Chemokine CX3CL1 MH - Chemokines/*biosynthesis MH - Chemokines, CX3C/biosynthesis MH - Connective Tissue Growth Factor MH - DNA/metabolism MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Glomerular Mesangium/cytology/*metabolism MH - Immediate-Early Proteins/*antagonists & inhibitors MH - Intercellular Signaling Peptides and Proteins MH - Lipoxins/*pharmacology MH - Membrane Proteins/biosynthesis MH - NF-kappa B/metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - Phosphorylation MH - Proto-Oncogene Proteins c-akt/metabolism MH - RNA, Messenger/analysis MH - Rats EDAT- 2006/01/13 09:00 MHDA- 2006/02/24 09:00 CRDT- 2006/01/13 09:00 PHST- 2006/01/13 09:00 [pubmed] PHST- 2006/02/24 09:00 [medline] PHST- 2006/01/13 09:00 [entrez] AID - S0085-2538(15)51459-2 [pii] AID - 10.1038/sj.ki.5000025 [doi] PST - ppublish SO - Kidney Int. 2006 Jan;69(2):248-56. doi: 10.1038/sj.ki.5000025.