Endogenous opioids modulate allograft rejection time in mice: possible relation with Th1/Th2 cytokines

Sacerdote, Paola; Secondo, V. E. M. Rosso Di San; Sirchia, G.; Manfredi, Barbara; Panerai, Alberto E.

doi:10.1046/j.1365-2249.1998.00680.x

Cited by 50 publications

(29 citation statements)

References 24 publications

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“…As a consequence of these regulatory circuits, -opioid receptors are preferentially expressed in type 2 but not type 1 T helper cells . Moreover, exogenous and endogenous -opioid ligands skew the T helper cell balance into the direction of type 2 T helper cells (Sacerdote et al, 1998(Sacerdote et al, , 2000Roy et al, 2001Roy et al, , 2004. It is interesting that the transcription of -opioid receptors in response to IL-4 is mediated by the transcription factors STAT6 and GATA3, which is typical for several genes expressed in type 2 T helper cells (Kraus et al, 2001;Börner et al, 2004b.…”

Section: Activation Of T Lymphocytes Induces -Opioid Receptors 501mentioning

confidence: 99%

T-Cell Receptor/CD28-Mediated Activation of Human T Lymphocytes Induces Expression of Functional μ-Opioid Receptors

Börner

Kraus²,

Bedini³

et al. 2008

Mol Pharmacol

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Opiates function as immunomodulators, partly by their effects on T cells. Opioids act via -, ␦-, and -opioid receptors, among which the -type is of particular interest, because morphine-like opioids preferentially bind to it. Here we report that -opioid receptor mRNA was induced after CD3/28-mediated activation of primary human T lymphocytes and Jurkat T cells, neither of which expresses the gene constitutively. Moreover, a reporter gene construct containing 2624 base pairs of the -opioid receptor promoter was transactivated by CD3/28 stimulation. Transcriptional induction of the -opioid receptor gene was mediated by activator protein-1 (AP-1), nuclear factor-B, and nuclear factor of activated T cells (NFAT). NFAT was found to bind to three sequences of the -opioid receptor promoter, located at nucleotides Ϫ1064, Ϫ785, and Ϫ486. Although the Ϫ486 element is in close proximity to a putative AP-1 site, there was no evidence for a combined AP-1/NFAT site. Furthermore, we demonstrated that the induction of interleukin-2 mRNA and protein in activated T cells was inhibited by morphine in cells, in which -opioid receptors had been induced by CD3/28 monoclonal antibodies (mAbs), and that this effect was blocked by the -opioid receptor-specific antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH 2 . CD3/28 mAb-induced interleukin-2 transcription was also inhibited by the opioids fentanyl and loperamide. This indicates that the induced -opioid receptor mRNA is translated into functional receptor protein. Furthermore, a -opioid receptor-enhanced green fluorescent protein-fusion protein was localized in membranes of Jurkat cells and internalized in response to [D-Ala 2 ,NMe-Phe 4 ,Gly 5 -ol]-enkephalin but not morphine. In conclusion, these data emphasize the role of opioids in the modulation of T lymphocyte signaling.

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Section: Activation Of T Lymphocytes Induces -Opioid Receptors 501mentioning

confidence: 99%

T-Cell Receptor/CD28-Mediated Activation of Human T Lymphocytes Induces Expression of Functional μ-Opioid Receptors

Börner

Kraus²,

Bedini³

et al. 2008

Mol Pharmacol

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“…The opioid receptor antagonist naloxone has been shown to enhance Th1-mediated responses, including skin graft rejection, in a murine model (12). In these studies, naloxone increased the production of IL-2 and IFN-␥ by splenocytes to promote rejection, indicating that endogenous ␤-endorphin normally inhibits IFN-␥ production.…”

mentioning

confidence: 90%

Chronic Morphine Treatment Promotes Specific Th2 Cytokine Production by Murine T Cells In Vitro via a Fas/Fas Ligand-Dependent Mechanism

Greeneltch

Kelly-Welch

Shi³

et al. 2005

The Journal of Immunology

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Improper homeostasis of Th1 and Th2 cell differentiation can promote pathological immune responses such as autoimmunity and asthma. A number of factors govern the development of these cells including TCR ligation, costimulation, death effector expression, and activation-induced cell death (AICD). Although chronic morphine administration has been shown to selectively promote Th2 development in unpurified T cell populations, the direct effects of chronic morphine on Th cell skewing and cytokine production by CD4+ T cells have not been elucidated. We previously showed that morphine enhances Fas death receptor expression in a T cell hybridoma and human PBL. In addition, we have demonstrated a role for Fas, Fas ligand (FasL), and TRAIL in promoting Th2 development via killing of Th1 cells. Therefore, we analyzed whether the ability of morphine to affect Th2 cytokine production was mediated by regulation of Fas, FasL, and TRAIL expression and AICD directly in purified Th cells. We found that morphine significantly promoted IL-4 and IL-13 production but did not alter IL-5 or IFN-γ. Furthermore, morphine enhanced the mRNA expression of Fas, FasL and TRAIL and promoted Fas-mediated AICD of CD4+ T cells. Additionally, blockade of Fas/FasL interaction by anti-FasL inhibited the morphine-induced production of IL-4 and IL-13 and AICD of CD4+ T cells. These results suggest that morphine preferentially enhances Th2 cell differentiation via killing of Th1 cells in a Fas/FasL-dependent manner.

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“…Previous studies (Sacerdote in 1998 and revealed that naloxone as an opioid antagonist is able to trigger the immune response to the Th1 pattern, and is also able to strengthen immune responses after vaccination (24,25). Jamali et al observed that naloxone can increase the levels of IFN-γ cytokine and cellular immune responses against herpes simplex virus infection, and hypothesized the possibility of adjuvant effect of naloxone on HSV-I vaccine (27).…”

Section: Hbs-nlx10mentioning

confidence: 99%

“…During the last decade, many studies have used this agent as adjuvant in the formulation of different vaccines. They showed that naloxone can induce TH1 pattern of immunity and increase the IFN-γ level (14,16,22,(24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

Immune Responses of Mice Immunized with HBsAg Formulated in Naloxone/Alum Mixture: Comparison to Fendrix Vaccine

et al. 2017

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Background: Hepatitis B virus (HBV) can cause cirrhosis of the liver and hepatocellular carcinoma. Due to the lack of sufficient immune response in whole population, several studies have been conducted to improve the efficacy of alum-based HBV vaccine. Here, naloxone/alum mixture as adjuvant was used for the hepatitis B surface antigen HBsAg vaccine and immune parameters evaluated in immunized mice. Objectives: The present study aimed at investigating the effect of naloxone/alum mixture for the HBsAg vaccine and comparing to Fendrix vaccine. Methods: Female Balb/c mice were vaccinated at day 0, 14, and 28 with alum-based vaccine or naloxone/alum mixture vaccine in different doses. Naloxone/alum vaccine groups received a dose of 3, 6, or 10 mg/kg of naloxone (NLX) in the vaccine formulation. One group received routine HBsAg alum vaccine and another group received Fendrix vaccine. Some groups received naloxone plus HBsAg without alum and a group received HBsAg without adjuvant. Phosphate buffered saline (PBS), naloxone, and alum were also injected into the control groups separately. Finally, the naloxone/alum formulated vaccine was compared with the Fendrix and routine alum-based vaccine with respect to the levels of total anti-HBS antibody, IFN-γ, IL-4, IgG1, IgG2a, and the level of lymphocyte proliferation. Results:The level of total anti-HBS antibody in naloxone formulated vaccine was comparable with Fendrix. Meanwhile, IFN-γ/IL-4 ratio level was significantly higher in naloxone formulated vaccine groups versus mere vaccine group. IgG2a was also higher in the naloxone formulated vaccine groups. Conclusions: Based on the data presented in the present study, it was found that naloxone/alum mixture has the ability to shift the immune response towards Th1 pattern and potentially increase immunity against infections.

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Endogenous opioids modulate allograft rejection time in mice: possible relation with Th1/Th2 cytokines

Cited by 50 publications

References 24 publications

T-Cell Receptor/CD28-Mediated Activation of Human T Lymphocytes Induces Expression of Functional μ-Opioid Receptors

T-Cell Receptor/CD28-Mediated Activation of Human T Lymphocytes Induces Expression of Functional μ-Opioid Receptors

Chronic Morphine Treatment Promotes Specific Th2 Cytokine Production by Murine T Cells In Vitro via a Fas/Fas Ligand-Dependent Mechanism

Immune Responses of Mice Immunized with HBsAg Formulated in Naloxone/Alum Mixture: Comparison to Fendrix Vaccine

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