Coculture of human articular chondrocytes with peripheral blood mononuclear cells as a model to study cytokine-mediated interactions between inflammatory cells and target cells in the rheumatoid joint.
A model for the coculture of chondrocytes in gelified agarose with mononuclear cells was developed to serve as an in vitro equivalent for cytokine-mediated events at the cartilage-synovial pannus junction in destructive arthropathies. Chondrocytes cultured in agarose keep their phenotypic stability. They release cartilage-specific aggrecans into the surrounding artificial matrix. When activated with lipopolysaccharide for 1 h, mononuclear cells release Interleukin 1 beta and Tumor Necrosis Factor alpha, thereby stimulating the chondrocytes to produce Interleukin 6, to diminish incorporation of 35S into aggrecans, and to degrade these intercellular macromolecules. This coculture model is a useful tool for studying interactions between inflammatory cells and target cells. To demonstrate its usefulness, the effect of three anti-inflammatory drugs (piroxicam, sulphasalazine, and hydrocortisone) on cytokine release by mononuclear cells, and subsequently on chondrocyte aggrecan metabolism was studied. The drugs were unable to abrogate Interleukin 1 and Tumor Necrosis Factor alpha release by activated mononuclear cells. Therefore, these pharmacological agents did not protect the artificial target tissue against cytokine-mediated degradation.
Malfait
A M
AM
Department of Rheumatology, University Hospital, Ghent, Belgium.
Verbruggen
G
G
Almqvist
K F
KF
Broddelez
C
C
Veys
E M
EM
D000328:Adult; D053674:Aggrecans; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology*; D002358:Cartilage, Articular / Q000166:cytology*; D002450:Cell Communication / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism / Q000502:physiology*; D016326:Extracellular Matrix Proteins; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism / Q000502:physiology; D037181:Lectins, C-Type; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010894:Piroxicam / Q000494:pharmacology; D011509:Proteoglycans / Q000378:metabolism; D012460:Sulfasalazine / Q000494:pharmacology; D013455:Sulfur / Q000378:metabolism; D013462:Sulfur Radioisotopes; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D053674:Aggrecans; D016207:Cytokines; D016326:Extracellular Matrix Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D011509:Proteoglycans; D013462:Sulfur Radioisotopes; D014409:Tumor Necrosis Factor-alpha; D010894:Piroxicam; D012460:Sulfasalazine; D013455:Sulfur; D006854:Hydrocortisone