It becomes a critical determinant for the attenuation of TLR4-initiated apoptosis byβ-arrestin 2. Taken together, we demonstrate that the TLR4 possesses the capability of accelerating GSK-3βactivation thereby deteriorating SD-induced apoptosis;β-arrestin 2 represents an inhibitory effect on TLR4-mediated apoptotic cascade, through controlling the homeostasis of activation and inactivation of GSK-3p. Stress, either physical or psychological,

can modulate immune function. However, the mechanisms associated with stress-induced immune suppression remains to be elucidated. P-arrestin 有 2 serves as adaptors, scaffolds, and/or signal transducers. The role ofβ-arrestin 2 in stress-induced immune suppression is not known yet. Here, we demonstrate thatβ-arrestin 2 deficiency in mice increases the sensitivity of chronic stress-induced lymphocyte

reduction. Interestingly, the stress-induced suppression of T help 1 (Th1) cytokine and increased production of Th2 cytokine was greatly increased in P-arrestin 2 deficient mice compared with wild type mice. Moreover, inhibition of PI3K in P-arrestin 2-deficient mice exerts an additive effect on stress-induced lymphocyte reduction. Our study thus 一般 demonstrates thatβ-arrestin 2 plays an important role in stress-induced immune suppression. Background:Although it is established that opioid and Mycobacterium tuberculosis are both public health problems, the mechanisms by which they affect lung functions remain elusive. Methodology/Principal Findings:We report here that mice subjected to chronic morphine administration and M. tuberculosis infection exhibited significant apoptosis in the lung in selleck wild type mice as demonstrated by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay. Morphine and M. tuberculosis significantly induced the expression of Toll-like

receptor 9 (TLR9), a key mediator of innate immunity and inflammation. Interestingly, deficiency in TLR9 significantly inhibited the morphine and M. tuberculosis induced apoptosis in the lung. In addition, chronic morphine treatment and M. tuberculosis infection enhanced the levels of cytokines (TNF-a, IL-1β, and IL-6) in wild type mice, but not in TLR9 knockout (KO) mice. The bacterial load was much lower in TLR9 KO mice compared with that in wild type mice following morphine and M. tuberculosis treatment. Morphine alone did not alter the bacterial load in either wild type or TLR9 KO mice. Moreover, administration of morphine and M. tuberculosis decreased the levels of phosphorylation of Akt and GSK3βin the wild type mice, but not in TLR9 KO mice, suggesting an involvement of Akt/GSK3p in morphine and M. tuberculosis-mediated TLR9 signaling. Furthermore, administration of morphine and M.