A stress sensor, IRE1α, is required for bacterial-exotoxin-induced interleukin-1ß production in tissue-resident macrophages.

Cholera toxin (CT), a bacterial exotoxin composed of one A subunit (CTA) and five B subunits (CTB), functions as an immune adjuvant. CTB can induce production of interleukin-1ß (IL-1ß), a proinflammatory cytokine, in synergy with a lipopolysaccharide (LPS), from resident peritoneal macrophages (RPMs) through the pyrin and NLRP3 inflammasomes. However, how CTB or CT activates these inflammasomes in the macrophages has been unclear. Here, we clarify the roles of inositol-requiring enzyme 1 alpha (IRE1α), an endoplasmic reticulum (ER) stress sensor, in CT-induced IL-1ß production in RPMs. In RPMs, CTB is incorporated into the ER and induces ER stress responses, depending on GM1, a cell membrane ganglioside. IRE1α-deficient RPMs show a significant impairment of CT- or CTB-induced IL-1ß production, indicating that IRE1α is required for CT- or CTB-induced IL-1ß production in RPMs. This study demonstrates the critical roles of IRE1α in activation of both NLRP3 and pyrin inflammasomes in tissue-resident macrophages.

Investigation of the Effect of Puncture Order and Position on the Difficulty of Lower and Middle Abdominal Port Placement.

Objectives: Port placements at the mid-abdomen (mainstay of robotic surgery [Rob]) appear to be difficult compared to that at lower abdomen (mainstay of conventional laparoscopy [Con-Lap]). We hypothesized that the reason for this may be the difference in port puncture places. Materials and Methods: We examined how the differences between the place and puncture order of ports affected Con-Lap cases with ports mainly placed in the lower abdomen and Rob cases with ports mainly placed in the middle abdomen. The trocar time was measured from the time when the puncture position and skin incision were determined and initiated, respectively, to the time when the port was punctured and fixed and used as the indicator of difficulty. Results: In the Con-Lap group analysis, the trocar time of the left lower port was longer (right lower: 77 s, middle lower: 117.5 s, and left lower: 138 s, P < 0.0001). In the Rob group analysis, the trocar time of the left most port was significantly longer (right-most: 89.0 s, right-middle: 92.5 s, left-middle: 121.0 s, and left-most: 197.0 s; P < 0.0001). In addition, the total trocar time was significantly longer in the first puncture at the right-middle port in the Rob group (right-most first: 8.4 min, right-middle first: 12.4 min, and left-middle first: 8.5 min, P = 0.0063). Conclusion: In the mid-abdomen port placement, mainstay of Rob cases, the puncture order, and port site have a significant impact on the difficulty of the procedure. It is preferable to avoid initially puncturing the right-middle port in case of the Rob.