Table 2.

The top five canonical signal transduction pathways affected by estradiol in activated systemic lupus erythematosus (SLE) T cells.

Pathway	SLE + E vs SLE − E	Shared downstream genes (pathway)
1- T helper cell differentiation	2.7 × 10−8	TGF-β1 (1, 2, 3, 4)
2- Glucocorticoid Receptor Signaling	1.1 × 10−7	TNF (1, 2, 3, 4, 6)
3- Role of macrophages, fibroblasts, and, endothelial cells in rheumatoid arthritis	1.5 × 10−7	IL-21 (1, 3, 4) NFATC3 (2, 5, 6)
4- Role of cytokines in mediating commmnicalion between immune cells	1.9 × 10−6	RAF1 (2, 5)
5- Phospholipase C Signaling	3.2 × 10−6
6- SLE signalinga	4.8 × 10−3

SLE T cell samples (n = 9) were cultured without and with estradiol. The T cells were activated as described in the text. Changes in global gene expression was profiled using microarray analysis. Gene lists were generated from the microarray data and pathways that were altered by estradiol were identified by Ingenuity Pathway Analysis. The p-value of overlap is shown for each pathway. Major downstream genes affected by estradiol treatment were variably shared among the pathways (shown in parentheses).

^aAlthough the canonical SLE signal transduction pathway was affected by estradiol it was not within the top five.