Rosmarinic acid down-regulates the LPS-induced production of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha) via the MAPK pathway in bone-marrow derived dendritic cells.
In the present study, we investigated whether rosmarinic acid, which has been suggested to exhibit anti-inflammatory properties, can suppress the expressions of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha) via the MAPK pathway in LPS-stimulated bone marrow-derived dendritic cells (BMDCs) in the presence of GM-CSF and IL-4 in media. The effects of rosmarinic acid were investigated in BMDCs with respect to the following; cytotoxicity, surface molecule expression, dextran-FITC uptake, cell migration, chemokine gene expression, and the MAPK signaling pathway. Rosmarinic acid was found to significantly inhibit the expressions of CD80, CD86, MHC class I, and MHC class II in LPS-stimulated mature BMDCs, and rosmarinic acid-treated BMDCs were found to be highly efficient with regards to antigen capture via mannose receptor-mediated endocytosis. In addition, rosmarinic acid reduced cell migration by inducing the expression of a specific chemokine receptor on LPS-induced mature BMDCs. Rosmarinic acid also significantly reduced the expressions of MCP-1 and MIP-lalpha induced by LPS in BMDCs and inhibited LPS-induced activation of MAPK and the nuclear translocation of NF-kappaB. These findings broaden current perspectives concerning our understanding of the immunopharmacological functions of rosmarinic acid, and have ramifications that concern the development of therapeutic drugs for the treatment of DC-related acute and chronic diseases.
Kim
Hyung Keun
HK
Department of Orthopaedics, Chonnam National University, Hwasun Hospital, Chonnam 519-809, Korea.
Lee
Jae Joon
JJ
Lee
Jun Sik
JS
Park
Yeong-Min
YM
Yoon
Taek Rim
TR
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D054405:Chemokine CCL3 / Q000096:biosynthesis*; D002934:Cinnamates / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D053630:Depsides / Q000494:pharmacology*; D015536:Down-Regulation; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D021381:Protein Transport / Q000187:drug effects; D051996:Transcription Factor RelA / Q000378:metabolism; D000097123:Rosmarinic Acid
D018932:Chemokine CCL2; D054405:Chemokine CCL3; D002934:Cinnamates; D053630:Depsides; D008070:Lipopolysaccharides; D020928:Mitogen-Activated Protein Kinases; D051996:Transcription Factor RelA; D000097123:Rosmarinic Acid; C496534:Ccl3 protein, mouse