Attenuation of LPS-induced cyclooxygenase-2 and inducible NO synthase expression by lysophosphatidic acid in macrophages.

LPS can activate the inflammatory cascades by inducing various inflammatory mediators, such as prostaglandin E(2) (PGE(2)) resulting from cyclooxygenase-2 (COX-2), and NO produced by inducible NO synthase (iNOS). Lysophosphatidic acid (LPA) has been demonstrated to participate in inflammation. This study aimed to clarify the impact and the involving mechanisms of LPA on LPS-incurred inflammation in macrophages. First, LPA appeared to attenuate LPS-induced protein and mRNA expression of COX-2 and iNOS genes, as well as production of PGE(2) and NO. By using selective inhibitors targeting various signaling players, the inhibitory G protein alpha subunit (Gα(i)) seemed to be involved in the effect of LPA; p38, ERK and NF-κB were involved in the LPS-mediated COX-2/PGE(2) pathway; and p38, JNK, phosphoinositide-3-kinase and NF-κB were involved in the LPS-mediated iNOS/NO pathway. LPA was able to diminish LPS-induced phosphorylation of p38 and Akt, as well as NF-κB p65 nuclear translocation. By utilization of inhibitors of COX-2 and iNOS, there appeared to be no modulation between the COX-2/PGE(2) and the iNOS/NO signaling pathways. Our findings demonstrate a clear anti-inflammatory role of LPA acting via Gα(i) in LPS-mediated inflammatory response in macrophages, owing, at least in part, to its suppressive effect on LPS-induced activation of p38, Akt and NF-κB.

Subpedicle decompression and vertebral reconstruction for thoracolumbar Magerl incomplete burst fractures via a minimally invasive method.

STUDY DESIGN: Retrospective. OBJECTIVE: To evaluate the clinical and radiographical results. SUMMARY OF BACKGROUND DATA: The evolution of posterior approach for burst fractures was from long-segment to short-segment and then to monosegmental fixation. Decompression of the spinal cord is performed by anterior or posterior approaches. The technique attempts to decompress the spinal cord by a paramedian subpedicle approach, and simultaneous vertebral reconstruction with pile-up titanium spacers (subpedicle decompression and body augmentation [SpBA]) was developed. METHODS: Eighty patients with symptomatic single thoracolumbar Magerl incomplete burst fractures were included. After manual reduction, transpedicle body augmentation and shortsegment fixation (TpBA group) were performed in 38 patients and SpBA in 42 cases. The mean follow-up was 52.6 ± 18.7 (TpBA) and 42.1 ± 7.8 (SpBA) months, and the age was 57.9 ± 7.2 and 59.1 ± 8.3 years. Clinical and radiographical outcomes were analyzed. RESULTS: The operation time was 66 ± 11 (TpBA) versus 34.5 ± 5.5 (SpBA) minutes. The initial anterior vertebral correction was 46.8 ± 12.2% (TpBA) versus 53.2 ± 15.0% (SpBA) (P = 0.03) and the final correction was 44.0 ± 10.8% versus 51.5 ± 15.3% (P = 0.01). Initial corrections of the lateral Cobb angle were 22.3° ± 2.6° versus 22.8° ± 2.7° and the final corrections were 19.1° ± 3.4° versus 20.5° ± 2.9°. The VAS score was 7.7 ± 1.2 versus 7.9 ± 1.2 preoperatively and 2.2 ± 0.7 versus 1.8 ± 0.6 (P = 0.02) at the final visit. Seventy-five patients maintained or recovered to Frankel grade E. Three patients in the TpBA group and 2 in the SpBA group improved from grade C to D. Technical complications included 1 root overstretch in the SpBA group and one incomplete decompression in the TpBA group. CONCLUSION: SpBA is a safe and fast technique to treat Magerl incomplete burst fractures and leads to good clinical results. LEVEL OF EVIDENCE: N/A.

Cell cycle regulation by glucosamine in human pulmonary epithelial cells.

Airway epithelial cells play an important role against intruding pathogens. Glucosamine, a commonly used supplemental compound, has recently begun to be regarded as a potential anti-inflammatory molecule. This study aimed to uncover how glucosamine impacts on cellular proliferation in human alveolar epithelial cells (A549) and bronchial epithelial cells (HBECs). With trypan blue-exclusion assay, we observed that glucosamine (10, 20, 50 mM) caused a decrease in cell number at 24 and 48 h; with a flow cytometric analysis, we also noted an enhanced cell accumulation within the G(0)/G(1) phase at 24 h and induction of late apoptosis at 24 and 48 h by glucosamine (10, 20, 50 mM) in A549 cells and HBECs. Examination of phosphorylation in retinoblastoma (Rb) protein, we found an inhibitory effect by glucosamine at 20 and 50 mM. Glucosamine at 50 mM was demonstrated to elevate both the mRNA and protein expression of p53 and heme oxygenase-1 (HO-1), but also caused a reduction in p21 protein expression. In addition, glucosamine attenuated p21 protein stability via the proteasomal proteolytic pathway, as well as inducing p21 nuclear accumulation. Altogether, our results suggest that a high dose of glucosamine may inhibit cell proliferation through apoptosis and disturb cell cycle progression with a halt at G(0)/G(1) phase, and that this occurs, at least in part, by a reduction in Rb phosphorylation together with modulation of p21, p53 and HO-1 expression, and nuclear p21 accumulation.