To characterize the potential interaction between interleukin-6 (IL6), Janus kinase (JAK)-signal transducer and activator of transcription (STAT)-3 (JAK/STAT3) pathway, and Transforming growth factor beta (TGFβ)-3 , and to determine whether such cross-talk was a contributing factor in the dysregulation of type I collagen production in leiomyomas.

Laboratory study.

University research laboratory.

None.

Exposure of leiomyoma and myometrial cell lines to IL6 and STAT3 activators/inhibitors. Western immunoblot analysis and immunohistochemistry.

Expression of STAT3, pSTAT3, SOCS3, COL1A1, and TGFb3.

We observed that IL6 increased pSTAT3 as well as collagen1A1 in uterine leiomyoma cells. Direct activation of the JAK/STAT3 pathway increased collagen1A1 production in leiomyoma cells, whereas inhibition of the pathway significantly decreased collagen1A1 production. We further observed that modulation of the JAK/STAT3 pathway also increased the expression of TGFβ3 protein. Leiomyoma cells exposed to TGFβ3 demonstrated a significant decrease in pSTAT3 protein. Myometrial cells demonstrated a less sensitive response to STAT3 modulation and collagen production.

Cross-talk between the TGFβ pathway and JAK/STAT3 pathway contributes to the fibrotic nature of uterine leiomyomas.