Table 1.
The summary of the changes in the cytokine concentrations in pre-RA and RA patients.
The “pre-RA patients” indicates the individuals who are in a very early stage of RA or lack the symptoms of RA at the time of study but eventually are diagnosed with RA.
Table 2.
Gene expression datasets used in this study.
Fig 1.
The cytokine signalling network regulating expression of iNOS.
The network has two compartments; cytosol and nucleus. The nucleus is represented by the green-bordered box while the remaining network is within the yellow-bordered box representing cytosol. The yellow border represents the cell membrane. The network is constructed in CellDesigner and the following symbols therein are adapted: the light green rectangles are proteins, the green trapeziums are mRNAs, the yellow rectangles are genes, the pale yellow coloured structures on the cell membrane are receptors and the boxes with stacked proteins are the complexes. The blue lines ending with circles represent activation, brown lines ending with circles represent ubiquitination and the red lines represent inhibition. The black arrows denote state transition, the orange arrows denote transportation across compartments, the green arrows denote transcription and the pink arrows denote translation.
Table 3.
The maximum fold changes of the pathway genes corresponding to TNF-α, IL-1β pathways and few other transcription factors from our microarray data analysis.
Table 4.
The maximum fold changes of the pathway genes corresponding to IFN, IL-10, IL-6, TGF-β pathways and AP-1 transcription factor from our microarray data analysis.
Fig 2.
The number of the synovial datasets in which the pathway genes corresponding to IFN, IL-10, IL-6 pathways are differentially expressed.
The green bars represent up-regulation of the genes in the datasets whereas the red bars represent their down-regulation.
Fig 3.
The number of the synovial datasets in which the pathway genes corresponding to TGF-β pathway are differentially expressed.
The green bars represent up-regulation of the genes in the datasets whereas the red bars represent their down-regulation.
Fig 4.
The number of the synovial datasets in which the pathway genes corresponding to TNF-α and IL-1β pathways are differentially expressed.
The green bars represent up-regulation of the genes in the datasets whereas the red bars represent their down-regulation.
Fig 5.
The number of the synovial datasets in which the pathway genes corresponding to transcription factors AP-1, Oct-1 and C/EBPβ are differentially expressed.
The green bars represent up-regulation of the genes in the datasets whereas the red bars represent their down-regulation.
Table 5.
The maximum fold changes of the pathway genes in macrophage dataset from our microarray data analysis.
Fig 6.
Hierarchical clustering of the individual samples based on the expressions of the network genes in GSE1919.
In this dataset, three RA patients and five controls were considered for the clustering after eliminating two pooled RA samples. The RA and the control samples clustered into separate groups. The medical therapies received by the patients are indicated in the figure.
Fig 7.
Hierarchical clustering of the individual samples based on the expressions of the network genes in GSE7307.
In this dataset, five RA patients and nine controls were considered for the clustering. The RA and the control samples clustered into separate groups.
Fig 8.
Hierarchical clustering of the individual samples based on the expressions of the network genes in GSE12021 (U133 A).
In this dataset, twelve RA patients and nine controls were considered for the clustering. One RA sample clustered together with the control samples whereas the other RA samples clustered separately. The medical therapies received by the patients are indicated in the figure. The medical therapies received by the patients are non-steroidal anti-rheumatic drug (NSARD), Azulfidine (AZ), Prednisolone (PS), Methotrexate (MTX), Cox-2 inhibitor (CX), Quensyl (QS), Tilidin (T) and non-steroidal anti-inflammatory drug (NSAID).
Fig 9.
Hierarchical clustering of the individual samples based on the expressions of the network genes in GSE12021 (U133 B).
In this dataset, twelve RA patients and four controls were considered for the clustering. One RA sample clustered together with the control samples. The medical therapies received by the patients are indicated in the figure. The medical therapies received by the patients are non-steroidal anti-rheumatic drug (NSARD), Azulfidine (AZ), Prednisolone (PS), Methotrexate (MTX), Cox-2 inhibitor (CX), Quensyl (QS), Tilidin (T) and non-steroidal anti-inflammatory drug (NSAID).
Fig 10.
Hierarchical clustering of the individual samples based on the expressions of the network genes in GSE55457.
In this dataset, thirteen RA patients and ten controls were considered for the clustering. One RA sample clustered together with the control samples whereas the other RA samples clustered separately. The medical therapies received by the patients are indicated in the figure. The medical therapies received by the patients are non-steroidal anti-rheumatic drug (NSARD), Azulfidine (AZ), Prednisolone (PS), Methotrexate (MTX), Cox-2 inhibitor (CX), Quensyl (QS), Tilidin (T) and non-steroidal anti-inflammatory drug (NSAID).
Fig 11.
Hierarchical clustering of the individual samples based on the expressions of the network genes in GSE55235.
In this dataset, ten RA patients and ten controls were considered for the clustering. The RA and the control samples clustered into separate groups. The medical therapies received by the RA patients are not specified in this dataset.
Fig 12.
Hierarchical clustering of the individual samples based on the expressions of the network genes in GSE10500.
In this dataset, five RA patients and three controls were considered for the clustering. The RA and the control samples clustered into separate groups.
Table 6.
Medical therapies received RA patients.
Fig 13.
The proposed model by which IFN/ IL-10 pathway mediates chronic inflammation in the RA synovium by elevating NO.
The coloured box with the black boundary is a representative cell in the RA synovium. The Y-shaped structures are the cytokine receptors and the rectangles within the cell are protein. The black arrows indicate either activation or production. The dotted black arrow indicates an unknown mechanism of JAK2 activation.
Table 7.
Up-regulation of STAT1 target genes.
The number of the synovial datasets in which the STAT1-target genes are up-regulated.