The interleukin-6 trans-signaling promotes progesterone production in human granulosa-lutein cells†.

As a critical paracrine regulator of multiple reproductive functions, the cytokine interleukin-6 (IL-6) is expressed in human granulosa cells and can be detected in follicular fluid. At present, the functional role of IL-6 in the regulation of ovarian steroidogenesis is controversial. Moreover, the detailed molecular mechanisms by which IL-6 regulates the production of progesterone in human granulosa cells remain to be elucidated. In the present study, we used primary and immortalized human granulosa-lutein (hGL) cells to investigate the effects of IL-6 on progesterone synthesis and the underlying molecular mechanisms. We found that IL-6 trans-signaling by the combined addition of IL-6 and soluble IL-6 receptor (sIL-6Rα)-induced steroidogenic acute regulatory expression and progesterone production in hGL cells. Additionally, IL-6/sIL-6Rα activated the phosphorylation of Janus activated kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), and the cellular effects were abolished by AG490 (JAK2 inhibitor), C188-9 (STAT3 inhibitor), or siRNA-mediated knockdown of STAT3. IL-6 trans-signaling-induced activation of JAK2/STAT3 also upregulated the expression of suppressor of cytokine signaling 3, which, in turn, negatively regulated the JAK2/STAT3 pathway by suppressing STAT3 activation and its downstream effects. Our findings provide insight into the molecular mechanisms by which IL-6 trans-signaling modulates steroidogenesis in hGL cells.

The interleukin 6 trans-signaling increases prostaglandin E2 production in human granulosa cells†.

As a potent autocrine regulator, the proinflammatory cytokine interleukin 6 (IL6) is expressed in granulosa cells and is involved in the modulation of various follicular functions, including follicular development and ovulation. At present, the detailed molecular mechanisms by which IL6 regulates the event of ovulation remain to be elucidated. In the present study, primary and immortalized (SVOG) human granulosa-lutein (hGL) cells were used to investigate the effects of IL6 on the expression of prostaglandin-endoperoxide synthase 2 (PTGS2) and the subsequent synthesis of prostaglandin E2 (PGE2) and to investigate the underlying molecular mechanisms. We found that instead of classic signaling, IL6/soluble form of the IL6 receptor (sIL-6Ralpha) trans-signaling induced the expression of PTGS2 and production of PGE2 in both SVOG cells and primary hGL cells. Moreover, IL6/sIL-6Ralpha activated the phosphorylation of Janus-activated kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), which in turn induced STAT3 nuclear translocation. In addition, these effects were suppressed by the addition of inhibitors (AG490 for JAK2 and C188-9 for STAT3) and by the small interfering RNA-mediated knockdown of STAT3. In addition, suppressor of cytokine signaling 3 (SOCS3) acts as a negative-feedback regulator in IL6/sIL-6Ralpha-induced cellular activities, including the activation and nuclear translocation of STAT3, upregulation of PTGS2 expression, and increase in PGE2 production in SVOG cells. In conclusion, IL6 trans-signaling upregulates the expression of PTGS2 and increases the production of PGE2 via the JAK2/STAT3/SOCS3 signaling pathway in hGL cells. Our findings provide insights into the molecular mechanisms by which IL6 trans-signaling may potentially modulate the event of ovulation in human ovaries.

Control Design and Digital Implementation of a Fast 2-Degree-of-Freedom Translational Optical Image Stabilizer for Image Sensors in Mobile Camera Phones.

This study presents design, digital implementation and performance validation of a lead-lag controller for a 2-degree-of-freedom (DOF) translational optical image stabilizer (OIS) installed with a digital image sensor in mobile camera phones. Nowadays, OIS is an important feature of modern commercial mobile camera phones, which aims to mechanically reduce the image blur caused by hand shaking while shooting photos. The OIS developed in this study is able to move the imaging lens by actuating its voice coil motors (VCMs) at the required speed to the position that significantly compensates for imaging blurs by hand shaking. The compensation proposed is made possible by first establishing the exact, nonlinear equations of motion (EOMs) for the OIS, which is followed by designing a simple lead-lag controller based on established nonlinear EOMs for simple digital computation via a field-programmable gate array (FPGA) board in order to achieve fast response. Finally, experimental validation is conducted to show the favorable performance of the designed OIS; i.e., it is able to stabilize the lens holder to the desired position within 0.02 s, which is much less than previously reported times of around 0.1 s. Also, the resulting residual vibration is less than 2.2-2.5 µm, which is commensurate to the very small pixel size found in most of commercial image sensors; thus, significantly minimizing image blur caused by hand shaking.