Norepinephrine potentiates proinflammatory responses of human vaginal epithelial cells

• Norepinephrine enhances the IL-6 and IL-8 responses of vaginal epithelial cells.
• The effects of NE are dependent on the presence of β2-adrenergic receptors.
• VIP and NPY mimic and augment the actions of NE, respectively.
• Human vaginal epithelial cells produce and secrete norepinephrine and dopamine.
• Neurotransmitters in the vaginal mucosa may contribute to immunomodulation.

The vaginal epithelium provides a barrier to pathogens and recruits immune defenses through the secretion of cytokines and chemokines. Several studies have shown that mucosal sites are innervated by norepinephrine-containing nerve fibers. Here we report that norepinephrine potentiates the proinflammatory response of human vaginal epithelial cells to products produced by Staphylococcus aureus, a pathogen that causes menstrual toxic shock syndrome. The cells exhibit immunoreactivity for catecholamine synthesis enzymes and the norepinephrine transporter. Moreover, the cells secrete norepinephrine and dopamine at low concentrations. These results indicate that norepinephrine may serve as an autocrine modulator of proinflammatory responses in the vaginal epithelium.