Lipopolysaccharide-Induced IL-1β Production by Human Uterine Macrophages Up-Regulates Uterine Epithelial Cell Expression of Human β-Defensin 2

Abstract

The uterine endometrium coordinates a wide spectrum of physiologic and immunologic functions, including endometrial receptivity and implantation as well as defense against sexually transmitted pathogens. Macrophages and epithelial cells cooperatively mediate innate host defense against bacterial invasion through the generation of immunologic effectors, including cytokines and antimicrobial peptides. In this study, we demonstrate that stimulation of peripheral blood monocytes and uterine macrophages with bacterial LPS induces the production of biologically active proinflammatory IL-1β. High doses of estradiol enhance LPS-induced IL-1β expression in an estrogen receptor-dependent manner. Furthermore, both peripheral blood monocyte- and uterine macrophage-derived IL-1β induce secretion of antimicrobial human β-defensin 2 by uterine epithelial cells. These data indicate dynamic immunologic interaction between uterine macrophages and epithelial cells and implicate a role for estradiol in the modulation of the immune response.

Crucial roles of binding sites for NF-κB and C/EBPs in IκB-ζ-mediated transcriptional activation

“…In addition to several cytokines, the present studies indicated that the hBD-2 and NGAL genes are targets for IκB-ζ -mediated transcription. Consistent with the induction spectrum of IκB-ζ , both the hBD-2 and NGAL genes are induced preferentially by IL-1β, but not by TNF-α in A549 human lung adenocarcinoma cells, keratinocytes and other cells [25][26][27][28][29][30]. A recent report has also shown critical roles for IκB-ζ in IL-1β-dependent induction of the genes [38].…”

“…In the present study, we analysed the molecular mechanisms of the IκB-ζ -mediated transcriptional activation. We focused on hBD-2 (human β-defensin 2) and NGAL (neutrophil gelatinase-associated lipocalin), both of which are preferentially induced by stimulators of TLR/IL-1 receptor signalling pathways, rather than by TNF-α [25][26][27][28][29][30]. We found that the promoters of both genes are synergistically activated by co-transfection of IκB-ζ and NF-κB.…”

Distinct Roles for Nod2 Protein and Autocrine Interleukin-1β in Muramyl Dipeptide-induced Mitogen-activated Protein Kinase Activation and Cytokine Secretion in Human Macrophages

“…IL-1R autocrine signaling has not been investigated downstream of other PRRs, with the exception of TLR4 (5-7) and TLR9 (5,6,8,9), to our knowledge. Given the dramatic contribution of autocrine IL-1␤ to Nod2 responses, we examined whether the loop contributes to cytokine secretion by multiple PRR.…”

“…MDP treatment activates NF-B and MAPK pathways and induces cytokines, including IL-1␤, in multiple human and mouse cell populations, including myeloid-derived cells (1)(2)(3)(4). Autocrine IL-1␤ is implicated in amplifying Tolllike receptor (TLR) cytokine induction, in particular by TLR4 (5-7) and TLR9 (5,6,8,9), however, the mechanism of this contribution is not well understood. The few reports addressing the IL-1␤ autocrine loop in Nod2 signaling have yielded mixed results.…”

The Role of Glucocorticoids in Pregnancy: Four Decades Experience with Use of Betamethasone in the Prevention of Pregnancy Loss

“…In chorionic explants MIF secretion is dose-dependently modulated by 17 -estradiol (E2) . As for progesterone, it favours the secretion of IL-3, IL-4, IL-5 and IL-10, that are reported to inhibit the Th1 response (Pioli et al, 2006). Interestingly, however, dydrogesterone induction of a Th1 to Th2 cytokine shift is also expressed by inhibition of IFN-and TNF-but up-regulation of the production of IL-4 and IL-6.…”