Adherence modifies the regulation of gene expression induced by interleukin-10.
Interleukin-10 (IL-10) is a well known anti-inflammatory cytokine. However, we previously showed that it could present pro-inflammatory properties on human monocytes in the absence of adherence. In the present study, using macroarray technology, we analyzed the effects of IL-10 and adherence on the expression of 1050 genes in human monocytes cultured for 3 hours on plastic or Teflon(R) (to avoid adherence). Adherence alone induced specifically the expression of 12 genes and repressed that of 25 genes. In adherent monocytes, IL-10 induced the expression of 21 genes and repressed that of 50 genes. In non-adherent monocytes, IL-10 induced the expression of 45 genes and repressed that of 67. Only 3 common genes were induced while 35 common genes were repressed by IL-10 in the two culture conditions. Interestingly, we showed that IL-10 modulated conversely on Teflon(R) and plastic the expression of 16 genes, of which SOCS molecules, coproporphyrinogen oxidase, matrix metalloproteinases and complement receptor-1 (CD35). This study demonstrates that adherence has profound modulatory effects on the properties and the signaling induced by IL-10. The discovery that IL-10 can inhibit the production of coproporphyrinogen oxidase (an enzyme involved in the synthesis of heme) may shed some lights on the mechanisms of anaemia induced by IL-10. Furthermore, the inhibition of the expression of SOCS1 by IL-10 in the absence of adherence, may explain its priming effects on a subsequent LPS stimulation that we previously described.
Petit-Bertron
Anne-France
AF
UP Cytokines and Inflammation, Institut Pasteur, 28 rue Dr. Roux, 75015 Paris, France.
Pedron
Thierry
T
Gross
Ulrich
U
Coppée
Jean-Yves
JY
Sansonetti
Philippe J
PJ
Cavaillon
Jean-Marc
JM
Adib-Conquy
Minou
M
D002448:Cell Adhesion; D002478:Cells, Cultured; D017364:Collagenases / Q000378:metabolism; D003304:Coproporphyrinogen Oxidase / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D053509:Matrix Metalloproteinase 13; D009000:Monocytes / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010969:Plastics / Q000494:pharmacology; D011138:Polytetrafluoroethylene / Q000494:pharmacology; D017463:Receptors, Complement 3b / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D008070:Lipopolysaccharides; D010969:Plastics; D017463:Receptors, Complement 3b; D016753:Interleukin-10; D011138:Polytetrafluoroethylene; D003304:Coproporphyrinogen Oxidase; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13