ABSTRACT
This study was performed to evaluate whether endocan expression, which is known to be involved in tumor angiogenesis, was increased in rheumatoid arthritic tissues. In addition, the involvement of adiponectin in the regulation of endocan expression in arthritic joints was examined. Arthritic synovial tissues from patients with rheumatoid arthritis (RA) or osteoarthritis (OA) were immunostained with antibodies to endocan and vascular endothelial growth factor (VEGF). Subsequently, synovial cells and human umbilical vein endothelial cells were cultured and stimulated with interleukin-1 ß (IL-1ß) or adiponectin. The mRNA and protein levels of endocan were evaluated by polymerase chain reaction and ELISA, respectively. Endocan expression was markedly increased in the inflammatory sites of RA synovial tissues. In OA tissues, endocan expression was higher in tissues displaying moderate and severe inflammation than in those with mild inflammation. In vitro expression levels of endocan and VEGF in endothelial and synovial cells were differentially increased in response to IL-1ß stimulation. Adiponectin was a more potent stimulant of endocan than IL-1ß at their respective physiological concentrations in synovial cells. Endocan silencing by small interfering RNA transfection of synovial cells decreased in vitro cell migration and invasion. In conclusion, adiponectin is an important factor in the stimulation of endocan expression in synovial cells. Adiponectin-induced endocan expression in synovial cells may stimulate cell migration and invasion as well as angiogenesis in the pannus of arthritic joints.
Subject(s)
Arthritis/genetics , Gene Expression , Neoplasm Proteins/genetics , Proteoglycans/genetics , Synovial Membrane/metabolism , Adiponectin/metabolism , Adiponectin/pharmacology , Arthritis/metabolism , Arthritis/pathology , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/metabolism , Arthritis, Rheumatoid/pathology , Cell Movement/drug effects , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Fibroblasts/drug effects , Fibroblasts/metabolism , Gene Knockdown Techniques , Humans , Immunohistochemistry , Neoplasm Proteins/metabolism , Osteoarthritis/genetics , Osteoarthritis/metabolism , Osteoarthritis/pathology , Proteoglycans/metabolism , RNA Interference , RNA, Small Interfering/genetics , Synovial Membrane/cytology , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolismABSTRACT
In an attempt to develop an antiinflammatory herbal remedy that is as potent as current synthetic medicines, the cortex of Phellodendron amurense Rupr (Rutaceae) and the rhizomes of Coptis chinensis Franch (Ranunculaceae) were combined in a 2:1 ratio. This ratio was chosen based on in vitro experiments and traditional Asian medicine prescriptions. The combined ethanol extract, named RAH13, was evaluated for antiinflammatory properties using animal models of acute inflammation such as the croton oil-induced ear edema test and an acetic acid-induced capillary permeability test. Models of chronic inflammation were also tested using the cotton pellet test and a delayed-type hypersensitivity (DTH) test. Oral administration of RAH13 at a dose of 200 mg/kg showed in vivo antiinflammatory activity as potent as the effects associated with 100 mg/mL of celecoxib or 1 mg/kg of dexamethasone. These effects were seen in both acute and chronic inflammation models, suggesting that RAH13 may be effective in controlling some inflammation-related diseases.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Coptis/chemistry , Disease Models, Animal , Inflammation/drug therapy , Phellodendron/chemistry , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Celecoxib , Dexamethasone/therapeutic use , Female , Granuloma/drug therapy , Male , Mice , Mice, Inbred BALB C , Mice, Inbred ICR , Phytotherapy , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Pyrazoles/therapeutic use , Sulfonamides/therapeutic useABSTRACT
Clematis mandshurica Rupr (Ranunculaceae) roots are used in traditional Korean medicine to treat inflammation-related diseases. Therefore, we undertook to investigate their inhibitory effect on inflammation under non-cytotoxic conditions. The ethanolic extract of Clematis mandshurica at 100 microg/ml was found to significantly block the production of the pro-inflammatory mediators, nitric oxide (NO) and prostaglandin E(2) (PGE(2)), in lipopolysaccharide (LPS)/interferon(IFN)-gamma-stimulated mouse peritoneal macrophages, by up to 77% and 59%, respectively. In addition, it significantly inhibited cell proliferation and cytokine production (interleukin (IL)-2 and IFN-gamma) in splenocytes stimulated with Con A (concanavalin A; 5 microg/ml). Furthermore, when splenocytes from extract fed mice (200 mg/kg for 2 weeks) were activated with Con A, cell proliferation and the production of IL-2 and IFN-gamma were significantly inhibited. In addition, the extract reduced in vivo inflammation in oxazolone-induced delayed type hypersensitivity (DTH) model mice. Taken together, these data suggest that Clematis mandshurica is able to ameliorate inflammatory disease by exerting an anti-inflammatory effect in cases of proinflammatory and cell-mediated inflammation.