1.Autophagy activation by interferon-γ via the p38 mitogen-activated protein kinase signalling pathway is involved in macrophage bactericidal activity.
Matsuzawa T1, Fujiwara E, Washi Y. Immunology. 2014 Jan;141(1):61-9. doi: 10.1111/imm.12168.
Macrophages are involved in many essential immune functions. Their role in cell-autonomous innate immunity is reinforced by interferon-γ (IFN-γ), which is mainly secreted by proliferating type 1 T helper cells and natural killer cells. Previously, we showed that IFN-γ activates autophagy via p38 mitogen-activated protein kinase (p38 MAPK), but the biological importance of this signalling pathway has not been clear. Here, we found that macrophage bactericidal activity increased by 4 hr after IFN-γ stimulation. Inducible nitric oxide synthase (NOS2) is a major downstream effector of the Janus kinase-signal transducer and activator of transcription 1 signalling pathway that contributes to macrophage bactericidal activity via nitric oxide (NO) generation. However, no NO generation was observed after 4 hr of IFN-γ stimulation, and macrophage bactericidal activity at early stages after IFN-γ stimulation was not affected by the NOS inhibitors, NG-methyl-l-arginine acetate salt and diphenyleneiodonium chloride.
2.Inhibition of phosphate-induced apoptosis in resting zone chondrocytes by thrombin peptide 508.
Zhong M1, Carney DH, Ryaby JT, Schwartz Z, Boyan BD. Cells Tissues Organs. 2009;189(1-4):56-9. doi: 10.1159/000152913. Epub 2008 Sep 1.
Growth plate chondrocytes are susceptible to apoptosis. Terminally differentiated chondrocytes are deleted via apoptosis, which primes the growth plate to vascular invasion and subsequent bone formation. Whether less differentiated resting zone chondrocytes are subject to the same mechanism that governs the apoptotic pathway of more differentiated growth zone chondrocytes is not known. In our current study, we demonstrated that inorganic phosphate, a key inducer of growth plate chondrocyte apoptosis, also causes apoptosis in resting zone chondrocytes, via a pathway similar to the one in growth zone chondrocytes. Our results demonstrated that the conditions that cause growth plate chondrocyte apoptosis lie in the external environment, instead of the differences in differentiation state.
3.Novel soluble guanylyl cyclase stimulator BAY 41-2272 attenuates ischemia-reperfusion-induced lung injury.
Egemnazarov B1, Sydykov A, Schermuly RT, Weissmann N, Stasch JP, Sarybaev AS, Seeger W, Grimminger F, Ghofrani HA. Am J Physiol Lung Cell Mol Physiol. 2009 Mar;296(3):L462-9. doi: 10.1152/ajplung.90377.2008. Epub 2008 Dec 12.
The protective effects of nitric oxide (NO), a physiological activator of soluble guanylyl cyclase (sGC), have been reported in ischemia-reperfusion (I/R) syndrome of the lung. Therefore, we studied the effects of BAY 41-2272, a novel sGC stimulator, on I/R injury of the lung in an isolated intact organ model. Lung injury was assessed by measuring weight gain and microvascular permeability (capillary filtration coefficient, K(fc)). Release of reactive oxygen species (ROS) into the perfusate was measured during early reperfusion by electron spin resonance (ESR) spectroscopy. Rabbit lungs were treated with BAY 41-2272, N(G)-monomethyl-L-arginine (L-NMMA), or NO to evaluate the effects on I/R-induced lung injury. In untreated lungs, a dramatic rise in K(fc) values and weight gain during reperfusion were observed, and these results were associated with increased ROS production. Both, BAY 41-2272 and L-NMMA significantly attenuated vascular leakage and suppressed ROS release.
4.Angiotensin II type 2 receptor-mediated and nitric oxide-dependent renal vasodilator response to compound 21 unmasked by angiotensin-converting enzyme inhibition in spontaneously hypertensive rats in vivo.
Brouwers S1, Smolders I, Massie A, Dupont AG. Hypertension. 2013 Nov;62(5):920-6. doi: 10.1161/HYPERTENSIONAHA.112.00762. Epub 2013 Sep 16.
Angiotensin II type 2 receptor (AT2R)-mediated vasodilation has been demonstrated in different vascular beds in vitro and in perfused organs. In vivo studies, however, consistently failed to disclose renal vasodilator responses to compound 21, a selective AT2R agonist, even after angiotensin II type 1 receptor blockade. Here, we investigated in vivo whether angiotensin-converting enzyme inhibition, reducing endogenous angiotensin II levels, could unmask the effects of selective AT2R stimulation on blood pressure and renal hemodynamics in normotensive and hypertensive rats. After pretreatment with the angiotensin-converting enzyme inhibitor captopril, intravenous administration of compound 21 did not affect blood pressure and induced dose-dependent renal vasodilator responses in spontaneously hypertensive but not in normotensive rats. The D1 receptor agonist fenoldopam, used as positive control, reduced blood pressure and renal vascular resistance in both strains.
