Polybacterial stimulation suggests discrete IL-6/IL-6R signaling in human fetal membranes: Potential implications on IL-6 bioactivity

Autor(es)

Noda-Nicolau, Nathalia Mayumi ^{[1, 2]} ; Polettini, Jossimara ^{[1, 2, 3]} ; da Silva, Marcia Guimaraes ^[2] ; Peltier, Morgan R. ^{[4, 5]} ; Menon, Ramkumar ^[1]

Afiliação do(s) autor(es)

^[1] Univ Texas Med Branch, Dept Obstet & Gynecol, Div Maternal Fetal Med & Perinatal Res, 301 Univ Blvd, MRB 11-158, Galveston, TX 77555 - USA

^[2] Univ Estadual Paulista, UNESP, Botucatu Med Sch, Dept Pathol, Botucatu, SP - Brazil

^[3] Univ Western Sao Paulo, UNOESTE, Masters Course Hlth Sci, Sao Paulo - Brazil

^[4] NYU, Winthrop Univ Hosp, Dept Biomed Res, Mineola, NY - USA

^[5] NYU, Winthrop Univ Hosp, Dept Obstet & Gynecol, Mineola, NY - USA

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF REPRODUCTIVE IMMUNOLOGY; v. 126, p. 60-68, APR 2018.
• Citações Web of Science: 1

Resumo

The polybacterial invasion of the amniotic cavity and risk of preterm birth is often due to cervicovaginal bacteria such as genital mycoplasmas (Mycoplasma hominis and Ureaplasma urealyticum) and Gardnerella vaginalis. The most studied biomarker associated with preterm birth is interleukin-6 (IL-6), a pleiotropic cytokine that performs different functions based on classical or trans-signaling mechanisms. This study evaluated the changes in IL-6 and IL-6 function associated accessory molecules by human fetal membranes to determine the functional availability of IL-6 assessment in an in vitro model of polybacterial infection. Fetal membranes were treated with LPS or heat-inactivated genital mycoplasmas and G. vaginalis alone or in combination. IL-6 and its soluble receptors (sgp130, sIL-6R) were assessed in conditioned medium by immunoassays and membrane-bound receptors were evaluated in the tissue using immunohistochemistry and RT-PCR. Data from protein and gene expression were evaluated using linear mixed effects models. Data from immunohistochemistry were evaluated using one-way analysis of variance followed by the Tukey test. Genital mycoplasmas alone, or in combination, inhibited IL-6 trans-signaling with increased sgp130 production. G. vaginalis activated the classical IL-6 signaling pathway, as did LPS. Polybacterial treatment resulted in a balanced response with neither pathway being favored. The increase in IL-6 production by fetal membranes in response to infection is likely a non-specific innate response and not an indicator of a functional mediator of any labor-inducing pathways. This suggests that correlating the risk of adverse pregnancy outcomes and designing interventions based on IL-6 levels without considering soluble receptors may be an ineffective strategy. (AU)

• Processo FAPESP: 12/17234-1 - Estudo in vitro de infecção das membranas corioamnióticas com espécies bacterianas isoladas do trato genital inferior e modulação da resposta imune inata na interface materno-fetal
• Beneficiário: Márcia Guimarães da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Regular