Fig. 1

Sex hormone effects in the expression of inflammatory mediators during bacterial infections. A schematic representation of the classic mechanism of action of progesterone (P4), estradiol (E2), and testosterone (T4) (for details, see the text), as well as the cross-talk with inflammatory signaling during bacterial infections is depicted. When bacterial virulence factors or pathogen-associated molecular patterns (PAMPs) are detected through host pattern recognition receptors such as Toll-like receptors (TLRs), signaling pathways are activated, allowing dissociation of the transcription factor NFκB from its inhibitor IκB, which is subsequently phosphorylated and degraded. Active NFκB is translocated into the nucleus and binds to response elements (NREs) of target genes, allowing the expression of pro-inflammatory genes. In general, P4 induces the expression of anti-inflammatory mediators and probably downregulates the expression of pro-inflammatory factors by sequestering NFκB and inhibiting its activity (indicated by a discontinued line arrow). On the other hand, during early response to infections or sepsis, E2 and T4 display a differential inflammatory effect, in which the former induces the expression of pro-inflammatory mediators by forming a complex with NFκB, and the latter promotes an anti-inflammatory effect. During late response to infections, E2 displays an anti-inflammatory response that prevents systemic damage, while T4 shows a persistent active pro-inflammatory response that triggers systemic damage (not shown). HR steroid hormone receptor, PR progesterone receptor, ER estrogen receptor, AR androgen receptor, HRE hormone response elements