Gene expression alterations of human peripheral blood monocytes induced by medium-term treatment with the TH2-cytokines interleukin-4 and -13.
The TH2-cytokines interleukins-4 and -13 severely alter gene expression of monocytic cells. We quantified the impact of interleukins-4 and -13 on the gene expression pattern of human peripheral blood monocytes applying a strategy that involved microarray hybridization, RT-PCR, immunohistochemistry and activity assays. After 3 days of continuous cytokine exposure the six most strongly upregulated gene products (15-lipoxygenase-1, fibronectin, monoamine oxidase-A, CD1c, CD23A, coagulation factor XIII) included four proteins with potential anti-inflammatory properties: (i) 15-lipoxygenase-1 (290-fold upregulation), (ii) fibronectin (180-fold upregulation), (iii) monoamine oxidase-A (56-fold upregulation) and (iv) coagulation factor XIII (35-fold upregulation). In addition, a number of other gene products, the expression of which is consistent with inflammatory resolution (annexin 1, collagen 1alpha2, laminin alpha5, TIMP3, heme oxygenase-1, CCL22, heat shock protein A8), were upregulated to a lower extent. In contrast, expression of classical pro-inflammatory gene products, such as tumor necrosis factor alpha, monocyte chemotactic protein-1, interleukins-1, -6, -8, -18, cyclooxygenase-2, as well as enzymes and receptors of the leukotriene cascade (5-lipoxygenase, 5-lipoxygenase activating protein, leukotriene B(4) receptor, cysteinyl leukotriene receptor 2) were significantly downregulated. These data suggest that medium-term treatment of human peripheral blood monocytes with interleukins-4/13 alters the gene expression pattern so that the cells might adopt a resolving phenotype.
Chaitidis
Pavlos
P
Institute of Biochemistry, University Clinics Charité, Humboldt University, Monbijoustrasse 2, 10117 Berlin, Federal Republic of Germany.
O'Donnell
Valerie
V
Kuban
Ralf J
RJ
Bermudez-Fajardo
Alexandra
A
Ungethuem
Ute
U
Kühn
Hartmut
H
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D015536:Down-Regulation; D015777:Eicosanoids / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D018793:Interleukin-13 / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D015289:Leukotrienes / Q000378:metabolism; D008084:Lipoxygenase / Q000378:metabolism; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018418:Th2 Cells; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D015777:Eicosanoids; D018793:Interleukin-13; D015289:Leukotrienes; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D008084:Lipoxygenase