Figure 6.

Cross-talk between interleukin 6 receptor (IL6R) and Toll-like receptor 4 (TLR4) signaling pathways in endometrial stromal cells during acute and chronic exposure to lipopolysaccharide (LPS). Acute exposure to LPS (1) activates nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways (2) and blocks STAT3α tyrosine phosphorylation (3) leading to the enhanced production of interkleukin (IL)-6 and IL-8 (4). IL-6 (5), through a positive feedforward loop via IL6R (6), results in tyrosine phosphorylation of STAT3α and sustained production of IL-6 and IL-8, putatively through activated Src kinase and ERK1/2 MAPK signaling pathways (7). The production of IL-6 and IL-8 is abrogated by inhibition of STAT3 or Src kinases, or by depletion of IL6R, STAT3, or SOCS3 with short interfering RNA (siRNA; red arrows indicate putative routes of cross-talk).