The activation and function of c-Jun N-terminal kinases (JNKs) were investigated in primary microglia cultures from neonatal rat brain, which express all three JNK isoforms. Lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), and thrombin preparations induced a rapid and lasting activation of JNKs in the cytoplasm. In the nucleus, the activation patterns were rather complex. In untreated microglia, the small pool of nuclear JNKs was strongly activated, while the high-affinity JNK substrate c-Jun was only weakly phosphorylated. Stimulation with LPS increased the total amount of nuclear JNKs and the phosphorylation of the transcription factor c-Jun. Levels of activated JNKs in the nucleus, however, rapidly decreased. Analysis of the nuclear JNK isoforms revealed that the amount of JNK1 declined, while JNK2 increased, and the weakly expressed JNK3 did not vary. This observation suggests that JNK2 is mainly responsible for the activation of c-Jun in this context. Upstream of JNKs, LPS induced a lasting activation of the constitutively present JNK kinase MKK4. The function of JNKs in LPS-triggered cellular reactions was investigated using SP600125 (0.5-5 microM), a direct inhibitor of JNKs. Inhibition of JNKs reduced the LPS-induced metabolic activity and induction of the AP-1 target genes cyclooxygenase-2 (Cox-2), TNF-alpha, monocyte chemoattractant protein-1 (MCP-1), and interleukin-6 (IL-6) in response to LPS, while ERK1/2 and p38 alpha had a more pronounced effect on LPS-induced cellular enlargement than JNKs. In summary, JNKs are essential mediators of relevant pro-inflammatory functions in microglia with different contributions of the JNK isoforms.
BackgroundInadvertently retained sponges and instruments still constitute a major but preventable complication in surgery. Given the high geographic mobility of patients, the fluctuation of physician-patient contact, and communication problems due to language barriers, the conscientious use of structured safety protocols in clinical routine is an essential aspect of quality in health care.Case presentationWe report the case of a 24-year-old refugee from Syria who presented at our gynecological outpatient department with a tumor in the lower abdomen, suspected to be a lump in the ovary or the uterus. Language barriers hindered exact recording of the patient’s medical history. We knew she had undergone three Caesarean sections several years ago. The diagnostic laparoscopy unexpectedly revealed a tumor suspected to be a retained surgical sponge. The lesion was removed completely and the patient discharged from the clinic five days later.ConclusionIn ambiguous cases, the diagnostic and therapeutic potential of minimally invasive surgery ensures safe and effective treatment of the patient, a short hospital stay, and low rates of complications. Especially in cases of language and/or cultural barriers, structured safety protocols should be a part of clinical routine in order to prevent unnecessary complications.
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