DESCRIPTION:

To further extend these studies to a large number of genes, mRNA profiles from IL-17A- and IL-17F-stimulated cells were studied using microarrays. The expression of several cell-specific markers was analyzed to characterize the population used in the experiment. Microarray-based comparison of IL-17A- and IL-17F-induced effects alone or in combination with TNF-􏰉. RA synoviocytes were stimulated with IL-17A or IL-17F (50 ng/ml) alone or in combination with TNF-􏰉 (0.5 ng/ml) for 12 h. Gene products that showed a signal intensity of 30 or greater were considered as ex- pressed and genes with a 2-fold or greater change were considered as regulated.

LABEL:

IL-17A and IL-17F

SCORE TYPE:

DATE ADDED:

2010-07-06

DATE UPDATED:

2020-05-06

SPECIES:

AUTHORS:

Zrioual S, Ecochard R, Tournadre A, Lenief V, Cazalis MA, Miossec P

TITLE:

Genome-wide comparison between IL-17A- and IL-17F-induced effects in human rheumatoid arthritis synoviocytes.

JOURNAL:

Journal of immunology (Baltimore, Md. : 1950) Mar 2009, Vol 182, pp. 3112-20

ABSTRACT:

IL-17A is implicated in rheumatoid arthritis (RA) pathogenesis; however, the contribution of IL-17F remains to be clarified. Using microarrays and gene-specific expression assays, we compared the regulatory effects of IL-17A and IL-17F alone or in combination with TNF-alpha on RA synoviocytes. IL-17A and IL-17F expression was studied in osteoarthritis and RA synovium by immunohistochemistry. The comparison between the IL-17A and IL-17F stimulatory effect on RA synoviocytes was assessed at the protein level by ELISA and at the mRNA level by microarrays and real-time RT-PCR. TNFRII expression was studied by real-time RT-PCR and immunofluorescence, and neutralizing Ab was used to analyze its contribution to CCL20 secretion. IL-17A and IL-17F were detected in plasma cell-like cells from RA but not osteoarthritis synovium. In microarrays, IL-17A and IL-17F alone had similar regulatory effects, IL-17F being quantitatively less active. Both cytokines induced a similar expression pattern in the presence of TNF-alpha. Based on a cooperation index, 130 and 203 genes were synergistically induced by IL-17A or IL-17F plus TNF-alpha, respectively. Among these, the new target genes CXCR4, LPL, and IL-32 were validated by real-time RT-PCR. IL-17A and IL-17F up-regulated TNFRII expression, but had no effects on TNFRI, IL-17RA or IL-17RC. TNFRII blockade inhibited the synergistic induction of CCL20 by IL-17A or IL-17F and TNF-alpha. IL-17A and IL-17F are both expressed in RA synovium. In the presence of TNF-alpha, they induced a similar expression pattern in RA synoviocytes. Accordingly, IL-17F appears as a target in Th17-mediated diseases such as RA. PUBMED: 19234208
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