ABSTRACT
Internalization of Staphylococcus aureus in bovine endothelial cells (BEC) is increased by tumor necrosis factor alpha stimulation and NF-κB activation. Because the phosphoinositide-3-kinase (PI3K)-Akt signaling pathway also modulates NF-κB activity, we considered whether the internalization of S. aureus by BEC is associated with the activity of PI3K and Akt. We found a time- and multiplicity of infection-dependent phosphorylation of Akt on Ser473 in BEC infected with S. aureus. This phosphorylation was inhibited by LY294002 (LY), indicating the participation of PI3K. Inhibition of either PI3K with LY or wortmannin, or Akt with SH-5, strongly reduced the internalization of S. aureus. Transfection of BEC with a dominant-negative form of the Akt gene significantly decreased S. aureus internalization, whereas transfection with the constitutively active mutant increased the number of internalized bacterium. Inhibition of PDK1 activity with OSU-03012 did not affect the level of S. aureus internalization, demonstrating that phosphorylation of Akt on Thr308 is not important for this process. Compared to the untreated control, the adherence of S. aureus to the surface of BEC was unaltered when cells were transfected or incubated with the pharmacological inhibitors. Furthermore, Akt activation by internalized S. aureus triggered a time-dependent phosphorylation of glycogen synthase kinase-3α (GSK-3α) on Ser21 and GSK-3ß on Ser9 that was partially inhibited with SH-5. Finally, treatment of BEC with LY prior to S. aureus infection inhibited the NF-κB p65 subunit phosphorylation on Ser536, indicating the involvement of PI3K. These results suggest that PI3K-Akt activity is important for the internalization of S. aureus and phosphorylation of GSK-3α, GSK-3ß, and NF-κB.
Subject(s)
Endothelial Cells/physiology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/physiology , Staphylococcus aureus/physiology , Animals , Cattle , Cells, Cultured , Glycogen Synthase Kinase 3/genetics , Glycogen Synthase Kinase 3/metabolism , Glycogen Synthase Kinase 3 beta , Interleukin-1beta/metabolism , Interleukin-1beta/pharmacology , NF-kappa B/metabolism , NF-kappa B/pharmacology , Phosphatidylinositol 3-Kinases/genetics , Phosphorylation , Proto-Oncogene Proteins c-akt/genetics , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/pharmacologyABSTRACT
We report a pelvic liposarcoma originating from the left spermatic cord that recurred following inadequate excision. In our case, the tumor was resected without performing orchiectomy previously. The patient was managed by laparoscopic resection, before undergoing radical orchiectomy in the left inguinal region. To our knowledge, no case of laparoscopic resection for the recurrent liposarcoma has been described. In addition, the present case serves to demonstrate that radical orchiectomy with wide excision is needed for paratesticular tumor.
Subject(s)
Genital Neoplasms, Male , Laparoscopy , Liposarcoma/surgery , Pelvic Neoplasms/surgery , Spermatic Cord , Aged , Genital Neoplasms, Male/pathology , Genital Neoplasms, Male/surgery , Humans , Liposarcoma/secondary , Male , Orchiectomy , Pelvic Neoplasms/diagnosis , Pelvic Neoplasms/secondary , Tomography, X-Ray ComputedABSTRACT
We report a pelvic liposarcoma originating from the left spermatic cord that recurred following inadequate excision. In our case, the tumor was resected without performing orchiectomy previously. The patient was managed by laparoscopic resection, before undergoing radical orchiectomy in the left inguinal region. To our knowledge, no case of laparoscopic resection for the recurrent liposarcoma has been described. In addition, the present case serves to demonstrate that radical orchiectomy with wide excision is needed for paratesticular tumor.