The zinc finger protein A20 is encoded by an immediate early response gene and acts as an inhibitor of nuclear factor (NF)-kappaB-dependent gene expression induced by different stimuli, including tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta). Toll-like receptor 2 (TLR2) and TLR4 have been found to transduce, respectively, peptidoglycan (PGN) and lipopolysaccharide (LPS) signals for the activation of NF-kappaB and the production of inflammatory cytokines. Here, we have examined the role of A20 in TLR-mediated NF-kappaB-dependent gene expression in human airway epithelial cells (AECs). Stimulation with LPS and PGN resulted in a significant increase in the level of A20 mRNA in primary cultured AECs and in NCI-H292 AECs. LPS and PGN induced activation of the IL-8 promoter both in NCI-H292 AECs and in HEK293 cells expressing either TLR2 or TLR4 plus MD-2. Dominant-negative myeloid differentiation protein and a mutant form of IkappaBalpha attenuated this PGN- or LPS-induced activation of the IL-8 promoter. Furthermore, overexpression of A20 inhibited activation of both NF-kappaB and the IL-8 promoter by PGN or LPS in these cells. Taken together, our results suggest that A20 may function as a negative regulator of TLR-mediated inflammatory responses in the airway, thereby protecting the host against harmful overresponses to pathogens.
Although further studies are needed to obtain a more complete understanding of gene expression and the role of MAPK in gene expression, the present results are important in understanding the molecular mechanisms involved in the response of bronchial epithelial cells to IV infection.
Schwannomas are tumors and commonly occur in the head and neck region; however, they rarely present in the retroperitoneum. A 79-year-old man was admitted to our hospital for a follow-up of a tumor in the hepatic hilus. A 2.8 × 2.5 cm solid tumor located between the hepatic hilus and common hepatic artery was originally identified, and the size of the tumor had increased from 2.0 × 2.0 cm to 2.8 × 2.5 cm over the course of 3 years. The patient underwent percutaneous sonopsy, and the tumor was subsequently diagnosed as a benign schwannoma. Since the patient wished to undergo an operation, we performed laparoscopic surgery. During the operation, the tumor was detected in the retroperitoneal space, where it was strongly adhered between the left gastric artery and common hepatic artery. At this point, no major vessels had vascularized the tumor. We then completely removed the tumor from the retroperitoneal space without any complications. The clinical course was uneventful, and the patient was discharged on postoperative day 4 without any symptoms. Later, a definitive histopathologic examination revealed a benign schwannoma. Here, we report this rare case of a retroperitoneal schwannoma located in the hepatic hilus.
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