Expression profiling of IL-10-regulated genes in human monocytes and peripheral blood mononuclear cells from psoriatic patients during IL-10 therapy.
Interleukin-10 (IL-10), originally identified as an inhibitor of pro-inflammatory cytokine production, exerts multiple immunomodulatory functions. Its ability to inhibit a Th1 response has been used in clinical trials for the treatment of inflammatory diseases including psoriasis. However, little is known about the molecular mechanisms of IL-10 functions. We aimed at identifying possible mediators of in vitro IL-10 treatment in monocytes by gene chip technology using Hu95a Affymetrix mRNA arrays with 12,000 genes. To prove relevance of the identified genes for the clinical situation we compared these in vitro results with genes being regulated by IL-10 in peripheral blood mononuclear cells from psoriatic patients undergoing IL-10 therapy. A high proportion of the 1,600 genes up-regulated and 1,300 genes down-regulated in vitro was found to be similarly regulated in vivo. Some genes, which were previously unknown to be regulated by IL-10, can be assigned to known IL-10 functions like e.g. the increase of pathogen clearance. Other new potentially immunomodulating genes have been identified to be regulated by IL-10, but their impact needs to be experimentally evaluated. We could confirm a recently reported up-regulation of heme oxygenase-1 (HO-1). However, we demonstrate that the anti-inflammatory mechanisms of IL-10 remain functional even when HO-1 is irreversibly inhibited.
Jung
Mechthild
M
Institute of Medical Immunology, Charité, Humboldt-University Berlin, Berlin, Germany.
Sabat
Robert
R
Krätzschmar
Jörn
J
Seidel
Henrik
H
Wolk
Kerstin
K
Schönbein
Christiane
C
Schütt
Sabine
S
Friedrich
Markus
M
Döcke
Wolf-Dietrich
WD
Asadullah
Khusru
K
Volk
Hans-Dieter
HD
Grütz
Gerald
G
D015703:Antigens, CD; D050976:Basic-Leucine Zipper Transcription Factors; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology; D007167:Immunotherapy; D016753:Interleukin-10 / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011565:Psoriasis / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology
D015703:Antigens, CD; C099359:BATF protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D018925:Chemokines; D016207:Cytokines; D004268:DNA-Binding Proteins; D006023:Glycoproteins; D007136:Immunoglobulins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D014157:Transcription Factors; D016753:Interleukin-10; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D006419:Heme Oxygenase (Decyclizing)