Cytokine-induced production of IFN-beta 2/IL-6 by freshly explanted human endometrial stromal cells. Modulation by estradiol-17 beta.
The cytokine IFN-beta 2/IL-6 has emerged as an important means of communication between cells--both within the immune system as well as outside it. In exploring the link between the endocrine and the immune systems, we have studied the secretion of IFN-beta 2/IL-6 by freshly explanted human endometrial stromal cells and its modulation by estrogens. Endometrial stromal cells produced IFN-beta 2/IL-6 in response to other inflammation-associated cytokines such as IL-1 alpha or beta, TNF, and IFN-gamma. This secretion was strongly inhibited by estradiol-17 beta at concentrations as low as 10(-9) M. Multiple species of stromal cell IFN-beta 2/IL-6 in the size range 23 to 30 kDa were detected using immunoprecipitation or immunoblotting procedures. The endometrial stromal cell IFN-beta 2/IL-6 species were phosphorylated and differentially glycosylated in a manner comparable to IFN-beta 2/IL-6 secreted by induced human peripheral blood monocytes or foreskin fibroblasts. However, in contrast to peripheral blood monocytes and fibroblasts, bacterial LPS did not induce IFN-beta 2/IL-6 production in endometrial stromal cells. Additionally, the IFN-beta 2/IL-6 identified in medium from IL-1 alpha-induced stromal cells is biologically active on hepatocytes. These observations, taken together with the observation that IFN-beta 2/IL-6 strongly inhibits the proliferation of human epithelial cells, suggest the possibility that stromal cell secreted IFN-beta 2/IL-6 may affect the physiology of the overlying epithelium in an hormonally modulated manner. Estrogen-regulated production of endometrial IFN-beta 2/IL-6 may participate in gender-specific systemic immunomodulation.
Tabibzadeh
S S
SS
Department of Pathology, City Hospital Center, Elmhurst, NY 11373.
Santhanam
U
U
Sehgal
P B
PB
May
L T
LT
D000328:Adult; D001685:Biological Factors / Q000494:pharmacology*; D046508:Culture Techniques; D016207:Cytokines; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis* / Q000302:isolation & purification / Q000502:physiology; D015850:Interleukin-6; D007378:Interleukins / Q000096:biosynthesis* / Q000302:isolation & purification / Q000502:physiology; D007700:Kinetics; D008875:Middle Aged; D010766:Phosphorylation
D001685:Biological Factors; D016207:Cytokines; D007370:Interferon Type I; D015850:Interleukin-6; D007378:Interleukins; D004958:Estradiol