Characterization of κ-opioid receptor transcripts expressed by T cells and macrophages

Alicea, Candido; Belkowski, Stanley M.; Sliker, Judith K.; Zhu, Jinmin; Liu‐Chen, Lee‐Yuan; Eisenstein, Toby K.; Adler, Martin W.; Rogers, Thomas J.

doi:10.1016/s0165-5728(98)00151-9

Cited by 42 publications

(19 citation statements)

References 36 publications

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“…Previous studies from this laboratory have demonstrated the expression of transcripts for the -opioid receptor in both primary thymocytes and two immature T cell lines (22,23). Subsequent work using a fluorescence-conjugated -opioid ligand have established the presence of -opioid receptors on each of the major subpopulations of developing T cells in the thymus (24).…”

Section: Discussionmentioning

confidence: 99%

“…We have recently demonstrated the expression of the -opioid receptor both in primary thymocytes and in a number of immature T cell lines, and our cloning and sequence analysis has revealed the expression of a number of intron-exon splice variants in these developing T cells (22,23). Subsequent flow cytometric analysis employing a fluorescent -opioid ligand suggests that the -opioid receptor is widely expressed within the thymus (24).…”

Section: Dichloro-n-methyl-n-[2-(1-pyrolidinyl)cyclohexyl]benzeneaceamentioning

confidence: 99%

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κ-Opioid Regulation of Thymocyte IL-7 Receptor and C-C Chemokine Receptor 2 Expression

Zhang

Rogers

2000

The Journal of Immunology

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Endogenous and exogenous κ-opioid agonists have been widely reported to modulate the immune response. We have published results that show that the superantigen-induced proliferative response of thymocytes is inhibited by the selective κ-opioid agonist trans-3,4-dichloro-N-methyl-N-[2-(1-pyrolidinyl)cyclohexyl]benzeneaceamide methanesulfonate (U50,488H). Previous work has established that the κ-opioid receptor is widely expressed within the thymus; however, little is known about the role of the κ-opioid receptor in the function of thymocytes. In the present report, we have examined the impact of U50,488H administration on the expression of cytokines in superantigen-stimulated thymocytes by RNase protection analysis. We have measured detectable levels of the cytokines IL-2, IL-4, IL-5, IL-13, and IFN-γ, and the chemokines lymphotactin and RANTES, in stimulated thymocyte cultures; however, addition of U50,488H did not alter the expression of these cytokines. Examination of cytokine receptor expression by these thymocytes revealed a significant inhibition in the expression of the transcript for the IL-7 receptor α-chain (IL-7Rα), and these results were confirmed by flow cytometry. Surprisingly, the expression of several other cytokine receptor chains including the common γ-chain, IL-2Rβ, or the IL-2Rα, IL-4Rα, and IL-15Rα chains, was not altered. In contrast to these results, a significant elevation in the expression of the chemokine receptor CCR2 was observed in U50,488H-treated cultures. These results suggest that the κ-opioid receptor may function to promote cellular migration at the expense of the sensitivity to the growth-promoting/maturation activity of IL-7.

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Section: Discussionmentioning

confidence: 99%

Section: Dichloro-n-methyl-n-[2-(1-pyrolidinyl)cyclohexyl]benzeneaceamentioning

confidence: 99%

κ-Opioid Regulation of Thymocyte IL-7 Receptor and C-C Chemokine Receptor 2 Expression

Zhang

Rogers

2000

The Journal of Immunology

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“…Their endogenous agonists are endomorphins 1 and 2, MET and leucine-enkephalin, and dynorphin, respectively, while ß-endorphin interacts with all opioid receptors. Opioid receptors are constitutively, or upon induction, expressed on the immune cells, and with respect to macrophages Ì, ‰ and Î receptor types (opioid receptor protein or transcript) were detected [23][24][25]. Opioid receptors cloned from the immune cells appeared to be identical to those from the neuronal cells [26].…”

Section: Introductionmentioning

confidence: 96%

Methionine-Enkephalin Stimulates Hydrogen Peroxide and Nitric Oxide Production in Rat Peritoneal Macrophages: Interaction of μ, δ and κ Opioid Receptors

Vujić

Stanojević

Dimitrijević

2004

Neuroimmunomodulation

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Objective: Methionine-enkephalin (MET) modulates various functions of macrophages related to both immune and inflammatory reactions in a naloxone reversible manner, suggesting that opioid receptors are involved in the regulation of macrophage activity. Since an endogenous opioid ligand might interact with more than one type of opioid receptor, the receptor interaction determines its effect on a particular function. Methods: In the present study we have investigated the involvement of different opioid receptor types/subtypes in MET-induced modulation of H₂O₂ and NO production in macrophages. Thioglycollate-elicited or resident rat peritoneal macrophages were treated in vitro with MET and/or specific antagonists of δ_1,2, δ₁, δ₂, µ and ĸ opioid receptors. Results: MET increased H₂O₂production inphorbol myristate acetate-stimulated rat peritoneal macrophages mainly through δ₁ opioid receptor. MET also enhanced NOproduction in rat peritoneal macrophages stimulated with lipopolysaccharide through δ₁ and µ opioid receptors. The blockade of µ and ĸ receptor facilitated a potentiating effect of MET on H₂O₂ release, and blockade of ĸ receptor further raised the MET-induced increase of NO production in macrophages. Conclusion: It is concluded that both negative and positive functional interaction between δ, µ and ĸ opioid receptors regulate the influence of MET on H₂O₂ and NO production in rat peritoneal macrophages.

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“…21,22 For example, the KOR agonist U50,488H blocks LPS-induced production of IL-1b, IL-6, and TNF-a in the macrophage cell line P388D1, an effect reversed by both opioid antagonist naloxone and the KORspecific antagonist norbinaltorphimine (NorB). 23 However, U50,488H failed to modulate the production of pro-inflammatory cytokines in a macrophage-derived cell line, RAW 264.…”

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confidence: 99%

β-arrestin protects neurons by mediating endogenous opioid arrest of inflammatory microglia

Feng

Burton

et al. 2013

Cell Death Differ

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Microglial activation worsens neuronal loss and contributes to progressive neurological diseases like Parkinson's disease (PD). This inflammatory progression is countered by dynorphin (Dyn), the endogenous ligand of the kappa-opioid receptor (KOR). We show that microglial b-arrestin mediates the ability of Dyn/KOR to limit endotoxin-elicited production of pro-inflammatory effectors and cytokines, subsequently protecting neurons from inflammation-induced neurotoxicity. Agonist-activated KOR enhances the interaction of b-arrestin2 with transforming growth factor-beta-activated kinase 1 (TAK1)-binding protein 1 (TAB1), disrupting TAK1-TAB1 mediated pro-inflammatory gene expression. We reveal a new physiological role for b-arrestin in neuroprotection via receptor internalization-triggered blockade of signal effectors of microglial inflammatory neurotoxicity. This result offers novel drug targets in the convergent KOR/b-arrestin2 and inflammatory pathways for treating microglial inflammatory neuropathologies like PD. Cell Death and Differentiation (2014) 21, 397-406; doi:10.1038/cdd.2013 published online 25 October 2013 Increasing evidence suggests that the overactivation of immune system-derived microglia in the substantia nigra (SN) is a key causative factor in the pathogenesis of Parkinson's disease (PD), the most prevalent neurodegenerative disease in the population over 60 years old. Pathologically, PD is characterized by the degeneration of dopaminergic (DA) neurons of the SN pars compacta (SNpc) in the midbrain, leading to disabled voluntary movements. Immunohistochemistry research has indicated that activated microglia accumulate around degenerating neurons in the SN of patients with PD and related parkinsonian syndromes. 1 Although microglial activation in these diseases is not limited to the SN, the DA neurons in the SN are particularly vulnerable to inflammatory insult owing to the larger population of microglia in the SN. 2,3 As a sensor of brain injury and aging, microglia's state and activity are regulated through neuronmicroglia communication involving the stimulation of signal transducing or phagocytic microglial receptors by neurotransmitters. 4,5 Deficiencies in this communication between neurons and microglia as a result of stress or aging leads to reactive microglia and prolonged inflammation and, as a result, neuronal death. Similarly, stimulation of microglia by bacteria or endotoxins results in outbursts of pro-inflammatory cytokines such as interleukin 1 beta (IL-1b), tumor necrosis factor-a (TNF)-a, and interleukin 6 (IL-6) through activation of toll-like receptor 4 (TLR4). This can contribute to the death of neurons in the SN because long-term inhibition of IL-1b and TNF-a has consistently been reported to attenuate tyrosine hydroxylase (TH þ ) neuron loss in PD models. 6,7 Meanwhile, neuron degeneration itself leads to further secondary activation of microglia via increased production of matrix metalloproteinase 3 and neuromelaine and, as a result, further neuronal death. [8][9][10] Thus...

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Characterization of κ-opioid receptor transcripts expressed by T cells and macrophages

Cited by 42 publications

References 36 publications

κ-Opioid Regulation of Thymocyte IL-7 Receptor and C-C Chemokine Receptor 2 Expression

κ-Opioid Regulation of Thymocyte IL-7 Receptor and C-C Chemokine Receptor 2 Expression

Methionine-Enkephalin Stimulates Hydrogen Peroxide and Nitric Oxide Production in Rat Peritoneal Macrophages: Interaction of μ, δ and κ Opioid Receptors

β-arrestin protects neurons by mediating endogenous opioid arrest of inflammatory microglia

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