Decidual cell biosynthesis of interleukin-6: Regulation by inflammatory cytokines

Intrauterine infection is an important cause of preterm labor and delivery and is characterized by increased production of inflammatory cytokines by gestational tissues. We have evaluated the biosynthesis of the inflammatory cytokine, interleukin-6 (IL-6), by human decidua and its regulation by other cytokines essential to the inflammatory process. We found that decidual cells secrete small amounts of IL-6 in the presence of growth medium supplemented only with 10% fetal calf serum. Interleukin 1 (α and β) and tumor necrosis factor (TNF) all induced a significant concentration-dependent stimulation of IL-6 production by decidual cells. Treatment of decidual cells with actinomycin D or cycloheximide abrogated the increase in IL-6 production induced by IL-1β. Northern blot analysis of cultured decidual cells revealed an increase in IL-6 messenger RNA (mRNA) over time in response to IL-1β. These data indicate that IL-1β stimulates an increase in IL-6 mRNA and protein production, reflecting either direct gene activation or stabilization of IL-6 mRNA. The concentration range tested (0.1 to 10 ng/mL) of each cytokine is within the range of values found in the amniotic fluid of women destined to deliver preterm due to infection of gestational tissues. Our data suggest that IL-6 is produced by human decidua in response to inflammation and, in conjunction with other inflammatory mediators, may play a role in the pathophysiology of preterm labor due to infection

Secretory immunoglobulin A: from mucosal protection to vaccine development.

Immune responses taking place in mucosal tissues are typified by secretory immunoglobulin A (S-IgA) molecules, which are assembled from proteins expressed in two cell lineages. The heavy and light chains as well as the J chain are produced in plasma cells, whereas the secretory component (SC) is associated to the immunoglobulin complex during transcytosis across the epithelial layer. S-IgA antibodies represent the predominant immunoglobulin class in external secretions, and the best defined entity providing specific immune protection for mucosal surfaces by blocking attachment of bacteria and viruses. S-IgA constitutes greater than 80% of all antibodies produced in mucosa-associated lymphoid tissues in humans. The existence of a common mucosal immune system permits immunization on one mucosal surface to induce secretion of antigen-specific S-IgA at distant sites. In addition, S-IgA antibodies not only function in external secretions, but also exert their antimicrobial properties within the epithelial cell during transport across the epithelium. Passive mucosal delivery of monoclonal IgA molecules neutralizes pathogens responsible for gastrointestinal and respiratory infections. Mucosal and systemic immunity can be achieved by orally administered recombinant S-IgA molecules carrying a protective bacterial epitope within the SC polypeptide primary sequence