Plasma membrane receptor mediated MAPK signaling pathways are activated in human uterine cervix at parturition

BACKGROUND: Cervical ripening resembles an inflammatory reaction. Estrogens induce leukocyte migration into tissue and factors promoting cervical remodeling and labor, although the mechanisms are only partially known. The aim of this study was to investigate whether plasma membrane receptor mediated pathways, known to be activated by estrogens and proinflammatory compounds, are involved in cervical ripening before labor. METHODS: The expression and distribution of mitogen activated protein kinases (MAPK), which transduce extracellular signals into intracellular responses through phosphorylation, and their intracellular targets transcription factors c-Jun and c-Fos proteins (AP-1) were analysed in cervical biopsies from term pregnant women (TP), immediately after parturition (PP), and from non-pregnant women (NP). Immunohistochemistry and RT-PCR techniques were used. RESULTS: Cell-specific alterations in the immunostaining pattern for MAPK were observed. The expressions of activated, phosphorylated MAPK forms pERK1/2, pJNK and p38MAPK were significantly increased in cervical stroma until TP and pERK1/2 expression was significantly enhanced in PP group. c-Jun was significantly increased in cervical stroma and smooth muscle in TP as compared to NP group. c-Fos was significantly increased in stroma, squamous epithelium and glandular epithelium in PP as compared to TP group. CONCLUSION: We report, for the first time, cell-specific activation of pMAPKs and their targets transcription factors c-Fos and c-Jun (AP-1) proteins in human uterine cervix until term pregnancy, and immediately after parturition. These results suggest a role for MAPK activation in cervical ripening before labor

Vascular and plaque imaging with ultrasmall superparamagnetic particles of iron oxide

Cardiovascular Magnetic Resonance (CMR) has become a primary tool for non-invasive assessment of cardiovascular anatomy, pathology and function. Existing contrast agents have been utilised for the identification of infarction, fibrosis, perfusion deficits and for angiography. Novel ultrasmall superparamagnetic particles of iron oxide (USPIO) contrast agents that are taken up by inflammatory cells can detect cellular inflammation non-invasively using CMR, potentially aiding the diagnosis of inflammatory medical conditions, guiding their treatment and giving insight into their pathophysiology. In this review we describe the utilization of USPIO as a novel contrast agent in vascular disease

Contribution of the p38(MAPK) signalling pathway to proliferation in human cultured airway smooth muscle cells is mitogen-specific

1. We have investigated the role of p38(MAPK) in human airway smooth muscle (HASM) proliferation in response to thrombin and bFGF. The regulation of cyclin D1 mRNA, cyclin D1, cyclin E and p21(Cip1) protein levels, and the extent of retinoblastoma protein (pRb) phosphorylation in response to activation of p38(MAPK) have also been examined. 2. Two distinct inhibitors of p38(MAPK), SB 203580 (10 μM) and SB 202190 (10 μM), prevented bFGF (0.3–3 nM)-stimulated cell proliferation, but had no effect on the response to thrombin (0.3–3 U ml(−1)). 3. In cells incubated with thrombin or bFGF for 20 h, there was an increase in p38(MAPK) phosphorylation in response to bFGF, but not to thrombin. Thrombin and bFGF-stimulated increases in ERK phosphorylation and cyclin D1 mRNA and protein levels were not influenced by SB 203580 pre-treatment. Similarly, cyclin E and p21(Cip1) protein levels, measured after 20 h incubation with mitogen, did not appear to be regulated by SB 203580 (10 μM). 4. Although both thrombin and bFGF significantly increased levels of pRb phosphorylation, SB 203580 (10 μM) inhibited only bFGF-stimulated pRb phosphorylation. In addition, SB 203580 (10 μM) selectively inhibited bFGF-stimulated DNA synthesis, suggesting that the antimitogenic actions of SB 203580 on pRb phosphorylation cause cell cycle arrest at late G1 phase. 5. In conclusion, these results indicate that p38(MAPK) is involved in bFGF-, but not in thrombin-stimulated HASM proliferation. The activation of the p38(MAPK) pathway by bFGF, but not by thrombin, regulates the phosphorylation of pRb without influencing cyclin D1 expression