ABSTRACT
Background and Objectives@#Epidemiological investigations have shown positive correlations between increased diesel exhaust particles (DEP) in ambient air and adverse health outcomes. DEP are the major constituent of particulate atmospheric pollution and have been shown to induce proinflammatory responses both in the lung and systemically. Here, we report the effects of DEP exposure on the properties of human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs), including stemness, regeneration, and immunomodulation. @*Methods@#and Results: Non-apoptotic concentrations of DEP (10 μg/ml) inhibited the migration and osteogenic differentiation capacity of WJ-MSCs. Gene expression profiling showed that DEP increased intracellular reactive oxygen species (ROS) and expression of pro-inflammatory and metabolic-process-related genes including cFos. Furthermore, WJ-MSCs cultured with DEP showed impaired suppression of T cell proliferation that was reversed by inhibition of ROS or knockdown of cFos. ERK inhibition assay revealed that DEP-induced ROS regulated cFos through activation of ERK but not NF-κB signaling. Overall, low concentrations of DEP (10 μg/ml) significantly suppressed the stemness and immunomodulatory properties of WJ-MSCs through ROS/ERK/cFos signaling pathways. Furthermore, WJ-MSCs cultured with DEP impaired the therapeutic effect of WJ-MSCs in experimental colitis mice, but was partly reversed by inhibition of ROS. @*Conclusions@#Taken together, these results indicate that exposure to DEP enhances the expression of pro-inflammatory cytokines and immune responses through a mechanism involving the ROS/ERK/cFos pathway in WJ-MSCs, and that DEP-induced ROS damage impairs the therapeutic effect of WJ-MSCs in colitis. Our results suggest that modulation of ROS/ERK/cFos signaling pathways in WJ-MSCs might be a novel therapeutic strategy for DEP-induced diseases.
ABSTRACT
Laryngoscopy and endotracheal intubation in patients undergoing general anesthesia causes hypertension and tachycardia with concomitant increases in plasma catecholamine concentration. These transient stress responses are greatly exaggerated in patients with hypertension and cardiovascular disease and can lead to cardiac arrhythmia, pulmonary edema, cardiac failure and cerebral hemorrhage. Therefore, several attempts have been made to attenuate the hypertensive and tachycardiac responses, but none have been satisfactory. This study was designed to evaluate verapamil or propranolol as a valuable adjuvant in attenuating hemodynamic responses to tracheal intubation in 53 patients with hypertension. They were randomly divided into three groups according to premedication used. Group 1 (n=19) was without pretreatment, and group 2 (n=18) and group 3 (n=16) were pretreated with verapamil (0.1 mg/kg) iv and verapamil (0. 1 mg/kg)-propranolol (0.01 mg/kg) mixture iv, respectively, just prior to the intubation. Mean arterial pressure (MAP) and heart rate (HR) were measured, just prior to intubation (baseline), after induction, and at 1, 2, 3, 4, 5 and 7 minutes following intubation. The results were as follows. 1) In the control group. tracheal intubation produced increases in MAP (27% average increase from baseline) and heart rate (31% increase) at one minute after the procedure. 2) In group 2, verapamil abolished pressor response to tracheal intubation, but did not affect tachycardiac responses. 3) In group 3, the verapamil-propranolol mixture attenuated both pressor and tachycardiac responses to tracheal intubation. 4) The rate-pressure product increased after tracheal intubation by 61% and 31% in group 1 and group 2, respectively, but it remained unchanged in group 3. These findings suggest that intravenous verapamil-propranolol mixture is a valuable adjuvant in attenuating hypertensive and tachyeardiac responses to tracheal intubation.