[show abstract][hide abstract] ABSTRACT: Chronic psychological stress has been shown to adversely impact immune system functions and compromise host defenses against various infections. However, the underlying mechanisms remain elusive. Recent studies have demonstrated that myeloid-derived suppressor cells (MDSCs) play an important role in regulating immunity. It is of interest to explore whether or not chronic psychological stress plays immunosuppressive functions partially by inducing MDSCs accumulation. In this work, we report that chronic psychological stress led to the accumulation of CD11b+Gr1+ cells in the bone marrow of BALB/c mice. Repeated β-agonist infusion showed no such effect. However, β-adrenergic blockade, but not glucocorticoids blockade, partially reversed the accumulation of CD11b+Gr1+ cells under the condition of chronic psychological stress, suggesting catecholamines collaborate with other factors to induce the accumulation. Further exploration indicates that cyclooxygenase 2 (COX-2)-prostaglandin E2 (PGE2) loop might act downstream to induce the accumulation. A majority of the accumulated CD11b+Gr1+ cells were Ly6G+Ly6C(low) immature neutrophils, which inhibited cytokine release of macrophages as well as T cell responsiveness. Moreover, the accumulated CD11b+Gr1+ cells under the condition of chronic psychological stress expressed multiple inhibitory molecules. Taken together, our data demonstrate for the first time that chronic psychological stress induces MDSCs accumulation in mice, which can contribute to immunosuppression.
PLoS ONE 01/2013; 8(9):e74497. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: The mitogen-activated protein kinase p38 plays key roles in cell progression, differentiation, inflammation, and apoptosis. p38 is activated by a variety of extracellular stimuli such as UV and proinflammatory cytokine tumor necrosis factor alpha (TNF-α). It has been demonstrated that destruction of microtubules with different reagents led to impaired p38 activation in response to various extracellular stimuli. However, several other groups have reported that microtubule-interfering agents stimulate the activation of MAPK superfamily members including p38 in certain cell context. The discrepancy suggests that destruction of microtubules stimulates the activation of MAPK superfamily members and thereby induces certain feedback inhibitor(s) of p38 signaling. In this article, we report that nocodazole, a widely used microtubule-interfering agent, antagonized UV- or TNF-α-induced p38 activation, even though this drug by itself weakly activated p38. The RNA synthesis inhibitor actinomycin D, but not p38-specific inhibitor SB203580, reversed the inhibitory effect of nocodazole on TNF-α-induced p38 activation. Nocodazole also weakly activated JNK, but significantly activated ERK. The inhibition by nocodazole of TNF-α-induced p38 activation was abolished by ERK-specific inhibitor U0126. Further exploration revealed that nocodazole significantly enhanced MKP-1 expression via the ERK activity. Thus, nocodazole increases the ERK activity to enhance MKP-1 expression which inhibits p38 activation induced by TNF-α.
Molecular and Cellular Biochemistry 02/2012; 364(1-2):373-80. · 2.33 Impact Factor