Klin Padiatr 2010; 222 - GNPI_FV_70
DOI: 10.1055/s-0030-1261407

Glucocorticoids potentiate IL-6 induced SP-B expression in H441 cells by enhancing the Jak/Stat signaling pathway

S Kunzmann 1, A Ladenburger 1, M Seehase 1, W Thomas 1, J Wirbelauer 1, BW Kramer 2, CP Speer 1
  • 1Universitäts-Kinderklinik im Luitpold-Krankenhaus, Würzburg
  • 2Universitäts-Kinderklinik, Maastricht, Niederlande

The respiratory distress syndrome (RDS) contributes to perinatal morbidity and mortality associated with preterm birth. Surfactant protein B (SP-B) is decreased in RDS. Both maternal antenatal steroid administration and chorioamnionitis reduce the incidence and severity of RDS. An important mediator in chorioamnionitis is interleukin-6 (IL-6) using the Jak-Stat signaling pathway for signaltransduction. We hypothesized that betamethasone (BTM) and dexamethasone (DEX) and IL-6 had synergistic effects on SP-B gene expression and Stat3 phosphorylation in H441 cells. DXM and BTM increased SP-B mRNA levels by 16.5 (13.3)-fold and IL-6 alone by 2.3-fold. After 48-hour exposure of cells to DXM or BTM, IL-6 caused a significantly greater increase in SP-B mRNA levels (28.1-fold) than IL-6 or glucocorticoids alone. While IL-6 stimulated tyrosine phosphorylation of Stat3 in a time- and dose dependent way, DXM and BTM had no effect on Stat3 phosphorylation. Both DXM and BTM could potentiate IL-6 induced phosphorylation of Stat3. The synergism of glucocorticoids and IL-6 on SP-B gene expression and the effect of glucocorticoids on IL-6 induced Stat3 phosphorylation could be blocked by a Jak-inhibitor. Expression level analysis showed that glucocorticoids increased the expression of the IL-6 binding a-subunit receptor (IL-6R). Our findings could represent an example of a pulmonary regulation-system in which one role of glucocorticoids is to increase the effect of a cytokine by up-regulation of its receptor. The described in vitro interaction of IL-6 and glucocorticoids could help explain the clinical observation that prenatal inflammation in preterm babies with antenatal steroid administration can attenuate severity of RDS.