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Substance P (SP) is well known for its immunoregulatory influence on NK cells. The biological actions of SP are mediated primarily through the high-affinity neurokinin-1 receptor (NK-1R), a G protein-coupled receptor (GPCR). Receptor binding triggers a cAMP signaling pathway and intracellular levels of cAMP are regulated via Gαs and Gαi. In this study NF449, a Gαs-selective G protein antagonist, was used to study the role of Gαs in the activation of NK92-MI cells by SP. Results show that 10(-12)M SP enhances the expression of Gαs and Gαi3 in NK92-MI cells promoting a cytotoxic phenotype characterized by expression of perforin and granzyme B. Development of a cytotoxic phenotype in NK92-MI cells stimulated with SP is blunted by inhibition of Gαs by NF449. In summary, SP signaling through NK-1R promotes a cytotoxic phenotype in NK92-MI cells characterized by upregulation of both Gαs and Gαi3. NF449 inhibits Gαs, blunts SP-induced expression of perforin and granzyme B, and represents a potential therapeutic avenue for reducing NK-cell mediated cytotoxicity.

Evidence from preclinical and clinical studies indicates that concentrations of cytokines are altered in sleep deprivation. However, data on the impact of sleep deprivation on concentrations of immunoglobulin and complement have received little scientific examination. The purpose of this study was to investigate the effects of 24h sleep deprivation on parameters of humoral immunity. Ten healthy volunteers (5 men and 5 women, 21-25 years old) stayed awake from 07:00 on day 1 until 07:00 on day 2 (sleep deprivation group), while another eight (4 men and 4 women, 21-23 years old) slept normally during the night (control group). Blood samples were drawn from the antecubital vein each day at 07.00. Parameters of humoral immunity, including serum IgG, IgA, IgM and C3, C4, were measured using an automatic analysis system. Experimental data showed that the levels of IgG, IgA, IgM and C3, C4 were all higher in the sleep-deprived group than in the control group (P

Substance P (SP) has been well known by its immunoregulatory properties on the functions of NK cells. However, the changes of molecules involved in the signaling pathways and effects of these molecules of NK92-MI cells activated by SP remain unclear. In this study, we explored the global changes in cellular protein expression of NK92-MI cells activated by SP by 2D-PAGE analysis. Subsequently, we demonstrated that 40 protein spots showed more than 2-fold changes, which displayed marked alterations with statistic significance (p0.05) between the testing group and control group. Compared with the control we also found that 16 proteins were up-regulated and 24 proteins were down-regulated among the 40 differentially expressed protein spots in the NK92-MI cells activated by SP. In addition 21 differentially expressed proteins were identified by MS/MS, suggesting that those proteins may play important roles in the process of activation of NK92-MI cells by SP. Moreover, the protein Rho GDI-2, Protein DJ-1 and alpha-enolase were reconfirmed by western blotting. Taken together, these findings may provide a new insight into better understanding at the molecular mechanisms of activation of NK92-MI cells by SP.

We set out to use proteomic profiling as a means of defining serum peptides that are indicative of a stress response related to an impact on the immune system. Two types of mouse models with the immune response impaired under stress (restraint stress and thermal stress) comprised the stressed groups (n = 10 in each group), while mice without stress represented the control group (n = 10). ProteinChip technology (surface-enhanced laser desorption/ionization time-of-flight mass spectrometry) was used to investigate the serum proteomic profiles. Histopathological examination of spleens from the stressed and control groups was performed to select appropriate individuals. Compared with the spleens of normal mice, those of mice subjected to restraint and thermal stress had decreased white pulp and lymphoid nodules, and their distribution and structure changed irregularly. Pathological changes occurred in all individuals in both stressed groups. The m/z values of the protein peaks ranged from 1,500 to 50,000 daltons and were mainly in the 2,000- to 20,000-dalton range. One hundred and fifty protein peaks were detected in the three groups. Four downregulated universal stress protein peaks with m/z of 4,389, 5,341, 5,526, and 6,252 were finally selected. Unexpectedly, no upregulated universal stress protein peaks were detected. These results suggested that impairment of the immune system results from inhibition of growth-promoting factors associated with the immune system. Identified protein peaks may be biomarkers of the impaired immune system under stress.

During the preparation of the manuscript, multiple sentences in the Introduction and Discussion sections were inappropriately copied from published reports ( Laura Redwine, Richard L. Hauger, J. Christian Gillin, Michael Irwin. 2000 Effects of sleep and sleep deprivation on interleukin-6, growth hormone, cortisol, and melatonin levels in humans. The Journal of Clinical Endocrinology & Metabolism. 85, 3597–3603. ). The authors regret the errors, and apologize to Redwine et al. All experimental data and conclusions remain solid. The correct Introduction and Discussion appear below and references cited are as in the original report.