Expression of β-endorphin in peripheral tissues after systemic administration of lipopolysaccharide as a model of endotoxic shock in mice

Kido, Ken’iti; Shindo, Yoichi; Toda, Shinichi; Masaki, Eiji

doi:10.1016/j.ando.2018.06.001

Cited by 7 publications

(3 citation statements)

References 27 publications

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“…Leukocytes (neutrophils, monocytes/macrophages, and lymphocytes) are a rich source of endogenous opioid peptides [ [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] ] that inhibit nociceptive transmission by binding to peripheral opioid receptors [ [14] , [15] , [16] ]. During inflammation, leukocytes are recruited to the site of damage [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Heme attenuates beta-endorphin levels in leukocytes of HIV positive individuals with chronic widespread pain

et al. 2020

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The prevalence of chronic widespread pain (CWP) in people with HIV is high, yet the underlying mechanisms are elusive. Leukocytes synthesize the endogenous opioid, β-endorphin, within their endoplasmic reticulum (ER). When released into plasma, β-endorphin dampens nociception by binding to opioid receptors on sensory neurons. We hypothesized that the heme-dependent redox signaling induces ER stress, which attenuates leukocyte β-endorphins levels/release, thereby increasing pain sensitivity in people with HIV. Results demonstrated that HIV positive individuals with CWP had increased plasma methemoglobin, erythrocytes membrane oxidation, hemolysis, and low plasma heme scavenging enzyme, hemopexin, compared to people with HIV without CWP and HIV-negative individuals with or without pain. In addition, the leukocytes from people with HIV with CWP had attenuated levels of the heme metabolizing enzyme, heme oxygenase-1, which metabolizes free heme to carbon-monoxide and biliverdin. These individuals also had elevated ER stress, and low β-endorphin in leukocytes. In vitro, heme exposure or heme oxygenase-1 deletion, decreased β-endorphins in murine monocytes/macrophages. Treating cells with a carbon-monoxide donor or an ER stress inhibitor, increased β-endorphins. To mimic hemolytic effects in a preclinical model, C57BL/6 mice were injected with phenylhydrazine hydrochloride (PHZ). PHZ increased cell-free heme and ER stress, decreased leukocyte β-endorphin levels and hindpaw mechanical sensitivity thresholds. Treatment of PHZ-injected mice with hemopexin blocked these effects, suggesting that heme-induced ER stress and a subsequent decrease in leukocyte β-endorphin is responsible for hypersensitivity in people with HIV.

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Section: Introductionmentioning

confidence: 99%

Heme attenuates beta-endorphin levels in leukocytes of HIV positive individuals with chronic widespread pain

et al. 2020

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“…Leukocytes (neutrophils, monocytes/macrophages, and lymphocytes) are a rich source of endogenous opioid peptides (5)(6)(7)(8)(9)(10)(11)(12)(13) that inhibit nociceptive transmission by binding to peripheral opioid receptors (14)(15)(16). During inflammation, leukocytes are recruited to the site of damage (17).…”

Section: Introductionmentioning

confidence: 99%

Heme Attenuates Endogenous Opioid Levels in Leukocytes of HIV positive individuals with Chronic Widespread Pain

Aggarwal

DeBerry

Ahmad

et al. 2020

Preprint

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The prevalence of chronic widespread pain (CWP) in people with HIV (PWH) is high, yet the underlying mechanisms are elusive. Leukocytes synthesize the endogenous opioid, β-endorphin (β-END), within their endoplasmic reticulum (ER). When released into plasma, β-END dampens nociceptive transmission by binding to opioid receptors on sensory neurons. In the present study, we hypothesized that heme-induced ER stress attenuates leukocyte levels/release of β-END, thereby increasing pain sensitivity in PWH. Results demonstrate that PWH with CWP have fragile erythrocytes, high plasma levels of cell-free heme, and impaired heme metabolism. Leukocytes from PWH with CWP also had high ER stress and low β-END compared to PWH without CWP and HIV-negative individuals with or without pain. In vitro heme exposure decreased β-END levels/secretion in murine monocytes/macrophages, which was prevented by treatment with sodium 4phenylbutyrate, an ER stress inhibitor. To mimic hemolytic effects in a preclinical model in vivo, C57BL/6 mice were injected with phenylhydrazine hydrochloride (PHZ). PHZ increased cell-free heme and ER stress, decreased leukocyte β-END levels and hindpaw mechanical sensitivity thresholds. Treatment of PHZ-injected mice with the heme scavenger, hemopexin, blocked these effects, suggesting that heme-induced ER stress and a subsequent decrease in leukocyte β-END may contribute to CWP in PWH.

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“…Um estudo in vitro, no qual células linfóides de camundongos foram tratadas com βendorfinas, demonstrou uma diminuição na produção de IL-1β, IL-2, TNF-α, e IFN-γ 48 . Em modelo de endotoxemia em camundongos mediante a administração de LPS foi evidenciado um incremento na expressão de RNAm pro-ópiomelanocortina em tecidos periféricos e um aumento na expressão de βendorfina em fígado e baço 49 .…”

Section: Ativação Celular Neuroinflamaçãounclassified

Efeito das catelicidinas na neuroinflamação tardia em modelo experimental de sepse

Flores¹

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Expression of β-endorphin in peripheral tissues after systemic administration of lipopolysaccharide as a model of endotoxic shock in mice

Cited by 7 publications

References 27 publications

Heme attenuates beta-endorphin levels in leukocytes of HIV positive individuals with chronic widespread pain

Heme attenuates beta-endorphin levels in leukocytes of HIV positive individuals with chronic widespread pain

Heme Attenuates Endogenous Opioid Levels in Leukocytes of HIV positive individuals with Chronic Widespread Pain

Efeito das catelicidinas na neuroinflamação tardia em modelo experimental de sepse

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