Receptor-mediated endocytosis and nuclear transport of human interleukin 1 <i>α</i>

Grenfell, S. J.; Smithers, Nick; Miller, Karen; Solari, Roberto

doi:10.1042/bj2640813

Cited by 78 publications

(40 citation statements)

References 61 publications

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“…Indeed, the microarray data revealed that IL-37 acts as an inhibitor of TLR and IL-1-mediated pathways, which confirms earlier findings 21 . Besides extracellular binding, IL-37 has been shown to translocate to the nucleus where it may act as a transcriptional modulator 28 , as is the case with nuclear translocation of another member of the IL-1 family member IL-1a 51,52 . Altogether, these mechanisms probably account for the anti-inflammatory actions of IL-37 in the adipose tissue.…”

Section: Discussionmentioning

confidence: 99%

IL-37 protects against obesity-induced inflammation and insulin resistance

et al. 2014

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Cytokines of the IL-1 family are important modulators of obesity-induced inflammation and the development of systemic insulin resistance. Here we show that IL-1 family member IL-37, recently characterized as an anti-inflammatory cytokine, ameliorates obesity-induced inflammation and insulin resistance. Mice transgenic for human IL-37 (IL-37tg) exhibit reduced numbers of adipose tissue macrophages, increased circulating levels of adiponectin and preserved glucose tolerance and insulin sensitivity after 16 weeks of HFD. In vitro treatment of adipocytes with recombinant IL-37 reduces adipogenesis and activates AMPK signalling. In humans, elevated steady-state IL-37 adipose tissue mRNA levels are positively correlated with insulin sensitivity and a lower inflammatory status of the adipose tissue. These findings reveal IL-37 as an important anti-inflammatory modulator during obesityinduced inflammation and insulin resistance in both mice and humans, and suggest that IL-37 is a potential target for the treatment of obesity-induced insulin resistance and type 2 diabetes.

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Section: Discussionmentioning

confidence: 99%

IL-37 protects against obesity-induced inflammation and insulin resistance

et al. 2014

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“…The downregulation of cytokine receptors through internalisation can help to decrease the beta cell toxicity of proinflammatory cytokines. Internalisation of the IL-1β receptor has been described in different cell types, where the internalised receptor accumulated in the cytosol and could be recycled to the plasma membrane [70,71,72]. Receptor-mediated endocytosis was also shown for IFN-γ, but in contrast to the recycling of the IL-1β receptor, a lysosomal ligandreceptor degradation occurred after internalisation [73].…”

Section: Discussionmentioning

confidence: 99%

Cytokines activate genes of the endocytotic pathway in insulin-producing RINm5F cells

et al. 2004

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Aims/hypothesis. Cytokines are important humoral mediators of beta cell destruction in autoimmune diabetes. The aim of this study was to identify novel cytokine-induced genes in insulin-producing RINm5F cells, which may contribute to beta cell death or survival. Methods. A global gene expression profile in cytokine-exposed insulin-producing RINm5F cells was achieved by automated restriction fragment differential display PCR. The expression of selected candidate genes was confirmed by real-time RT-PCR analysis. Results. Exposure of RINm5F cells to IL-1β or to a cytokine mixture (IL-1β, TNF-α, IFN-γ) for 6 h resulted in the differential expression of a functional gene cluster. Apart from the well-known up-regulation of the cytokine-responsive genes iNOS, NF-κB, MnSOD and Hsp70, several genes that belong to the functional cluster of the endocytotic pathway were identified. These endocytotic genes comprised: clathrin, megalin, synaptotagmin and calcineurin, which were up-regulated by IL-1β or the cytokine mixture.In contrast, the expression of the calcineurin inhibitor CAIN and of the GDP/GTP exchange protein Rab3 was down-regulated by cytokines. Other up-regulated cytokine-responsive genes were: agrin, murine adherent macrophage protein mRNA (MAMA) and transport-associated protein (TAP1/MTP), whereas the plasma membrane calcium ATPase (PMCA) 2 and PMCA 3 genes were down-regulated by cytokines. Conclusions/interpretation. Our results indicate that genes of the endocytotic pathway are regulated by pro-inflammatory cytokines. This might affect the density of cytokine receptors at the beta cell surface and concomitantly the sensitivity of the cells to cytokine toxicity. A better understanding of the functional cross-talk between endocytotic and cytokine signalling pathways could further the development of novel strategies to protect pancreatic beta cells against toxic effects of pro-inflammatory cytokines.

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“…10 (3) Both IL-1 and TNF-␣ have been shown to be internalized by a receptor-mediated process. 44,45 Suppression of TNF-␣-mediated E-selectin expression by PAO has been attributed to an inhibition of receptor-mediated endocytosis of TNF-␣. 30 Whether this mechanism can explain the observations with IL-1 remains to be established.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Tumor Necrosis Factor-α– and Interleukin-1–Induced Endothelial E-Selectin Expression by Thiol-Modifying Agents

Friedrichs

Müller

Brigelius‐Flohé

1998

ATVB

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Abstract-The expression of endothelial-leukocyte adhesion molecules has been postulated to be regulated by redoxsensitive events. Tumor necrosis factor-␣ (TNF-␣)-and interleukin-1 (IL-1)-induced E-selectin expression was analyzed after pretreating human umbilical vein endothelial cells with different thiol-modifying agents, ie, diamide, phenylarsine oxide, N-ethylmaleimide, and diethyl maleate. E-selectin protein expression was quantified by indirect immunofluorescence. All compounds suppressed the cytokine-induced E-selectin expression in a concentrationdependent manner, whereas the antioxidant N-acetylcysteine showed no effect. The inhibitory effect of diamide (100 mol/L, 1 hour) was reversible within 6 hours when the cells were allowed to recover before application of cytokines. Reversibility was strongly delayed when cells were deprived of glutathione by buthionine sulfoximine pretreatment. Glutathione depletion alone did not influence cytokine-induced E-selectin expression. Analysis of cellular glutathione status showed a 3-fold increase in oxidized glutathione after diamide treatment. Monochlorobimane labeling also revealed a decrease in total cellular thiols. During recovery, the glutathione status was restored within 1 hour, whereas total thiol content and E-selectin expression needed at least 6 hours to return to baseline. Complete inhibition of E-selectin expression by the vicinal thiol blocker phenylarsine oxide (0.5 mol/L) was reversed by dithiols like dithiothreitol or dimercaptopropanol, but not by the monothiol 2-mercaptoethanol. These data suggest that proteins with essential thiols, most probably vicinal thiols. are involved in the IL-1-and TNF-␣-mediated induction of E-selectin. These thiols must be in the reduced state; oxidation or other modification thereof attenuates or abolishes the cells' response to the cytokines.

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Receptor-mediated endocytosis and nuclear transport of human interleukin 1 α

Cited by 78 publications

References 61 publications

IL-37 protects against obesity-induced inflammation and insulin resistance

IL-37 protects against obesity-induced inflammation and insulin resistance

Cytokines activate genes of the endocytotic pathway in insulin-producing RINm5F cells

Inhibition of Tumor Necrosis Factor-α– and Interleukin-1–Induced Endothelial E-Selectin Expression by Thiol-Modifying Agents

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