Hierarchical control of interleukin 13 (IL-13) signals in lung fibroblasts by STAT6 and SOX11.

Interleukin (IL)-13 is a signature cytokine of type 2 inflammation important for the pathogenesis of various diseases, including allergic diseases. Signal transducer and activator of transcription (STAT) 6 is a critical transcriptional factor for the IL-13 signals; however, it remains unknown how expression of the IL-13-induced genes is differentiated by the transcriptional machineries. In this study, we identified IL-13-induced transcriptional factors in lung fibroblasts using DNA microarrays in which SOX11 was included. Knockdown of SOX11 down-regulated expression of periostin and CCL26, both of which are known to be downstream molecules of IL-13, whereas enforced expression of SOX11 together with IL-13 stimulation enhanced expression of periostin. Moreover, we found that in DNA microarrays combining IL-13 induction and SOX11 knockdown there exist both SOX11-dependent and -independent molecules in IL-13-inducible molecules. In the former, many inflammation-related and fibrosis-related molecules, including periostin and CCL26, are involved. These results suggest that SOX11 acts as a trans-acting transcriptional factor downstream of STAT6 and that in lung fibroblasts the IL-13 signals are hierarchically controlled by STAT6 and SOX11.

Comparison of RTPS and Monte Carlo dose distributions in heterogeneous phantoms for photon beams.

The purpose of this study was to compare dose distributions from three different RTPS with those from Monte Carlo (MC) calculations and measurements, in heterogeneous phantoms for photon beams. This study used four algorithms for RTPS: AAA (analytical anisotropic algorithm) implemented in the Eclipse (Varian Medical Systems) treatment planning system, CC (collapsed cone) superposition from the Pinnacle (Philips), and MGS (multigrid superposition) and FFT (fast Fourier transform) convolution from XiO (CMS). The dose distributions from these algorithms were compared with those from MC and measurements in a set of heterogeneous phantoms. Eclipse/AAA underestimated the dose inside the lung region for low energies of 4 and 6 MV. This is because Eclipse/AAA do not adequately account for a scaling of the spread of the pencil (lateral electron transport) based on changes in the electron density at low photon energies. The dose distributions from Pinnacle/CC and XiO/MGS almost agree with those of MC and measurements at low photon energies, but increase errors at high energy of 15 MV, especially for a small field of 3x3 cm(2). The FFT convolution extremely overestimated the dose inside the lung slab compared to MC. The dose distributions from the superposition algorithms almost agree with those from MC as well as measured values at 4 and 6 MV. The dose errors for Eclipse/AAA are lager in lung model phantoms for 4 and 6 MV. It is necessary to use the algorithms comparable to superposition for accuracy of dose calculations in heterogeneous regions.