Nonhematopoietic β-Arrestin-1 Inhibits Inflammation in a Murine Model of Polymicrobial Sepsis

Sharma, Deepika; Packiriswamy, Nandakumar; Malik, Ankit; Lucas, Peter C.; Parameswaran, Narayanan

doi:10.1016/j.ajpath.2014.05.002

Cited by 15 publications

(26 citation statements)

References 51 publications

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“…Equivalent proportion of neutrophils, lymphocytes, monocytes and eosinophils are observed in bone marrow 55 . Further splenic 11 , 56 , 57 , thymic 57 and blood 56 composition of immune cells is unaffected by loss of β-arrestins. Equivalent CSF-1 and F4/80 expression is observed in bone marrow derived macrophages (BMDMs) from WT or β-arrestin2 knockout mice 58 .…”

Section: β-Arrestins In Immune Systemmentioning

confidence: 96%

Multifaceted role of β-arrestins in inflammation and disease

Sharma

Parameswaran

2015

Genes Immun

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Arrestins are intracellular scaffolding proteins known to regulate a range of biochemical processes including G-protein coupled receptor (GPCR) desensitization, signal attenuation, receptor turnover and downstream signaling cascades. Their roles in regulation of signaling network have lately been extended to receptors outside of the GPCR family, demonstrating their roles as important scaffolding proteins in various physiological processes including proliferation, differentiation, and apoptosis. Recent studies have demonstrated a critical role for arrestins in immunological processes including key functions in inflammatory signaling pathways. In this review, we provide a comprehensive analysis of the different functions of the arrestin family of proteins especially related to immunity and inflammatory diseases.

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Section: β-Arrestins In Immune Systemmentioning

confidence: 96%

Multifaceted role of β-arrestins in inflammation and disease

Sharma

Parameswaran

2015

Genes Immun

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“…Sepsis can leads to accumulation of bacterial endotoxins, release of inflammatory mediators and immune dysfunction (22,23). Inflammatory responses are the major reason leading to mortality of patients with sepsis (24,25).…”

Section: Discussionmentioning

confidence: 99%

Inflammatory cytokine expression in patients with sepsis at an intensive care unit

2018

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Abstract. Sepsis is a systemic inflammatory response syndrome caused by infection of bacteria, fungi and/or viruses in clinical patients. It is known that inflammatory cytokine levels have an essential role in the progression of sepsis. The present study investigated the role of inflammatory markers in human peripheral blood mononuclear cells (hPBMCs) of patients with sepsis at an intensive care unit. In addition, the plasma levels of inflammatory cytokines were compared between sepsis patients and healthy individuals. The results demonstrated that the serum levels of interleukin-1, -17 and -6, as well as tumor necrosis factor-α, were upregulated in sepsis patients. The serum levels of high mobility group box 1 and C-reactive protein were increased in sepsis patients compared with those in healthy individuals. The expression levels of nuclear factor-κB-p65 and its inhibitor IκBα, as well as the ratio of CD25 + cells, and the levels of neutrophil gelatinase-associated lipocalin and peptidoglycan recognition protein were higher in hPBMCs in sepsis patients compared with those in healthy individuals. It was also indicated that balance of T helper type 1/2 cytokines was also disturbed in patients with sepsis compared with that in healthy individuals. In conclusion, these results indicated that inflammation is involved in the progression of sepsis by interfering with the expression of various molecules, suggesting a potential therapeutic strategy for the treatment of sepsis patients.

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“…5G, H). Given the important role that b-arrestin-1 plays in immune responses that are related to the TNF-a/D-GalN model (34)(35)(36), we examined the mRNA levels of several proinflammatory cytokines and chemokines in the livers of Arrb1 2/2 mice and WT littermates. Arrb1 2/2 mice demonstrated slightly decreased expression of most inflammatory genes (Supplemental Fig.…”

Section: B-arrestin-1 Suppresses Nf-kb Activity By Interfering With Tmentioning

confidence: 99%

NF‐κB directly regulates β‐arrestin‐1 expression and forms a negative feedback circuit in TNF‐α‐induced cell death

Guo

Wang

et al. 2018

FASEB j.

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β-Arrestins (β-arrestin-1 and -2) are multifunctional proteins that play important roles in the regulation of inflammation and cell survival that need to be tightly controlled; however, the mechanism that underlies their gene expression is largely unclear. Here, we demonstrate that β-arrestin-1 is a transcriptional target of NF-κB. mRNA and protein levels of β-arrestin-1 were up-regulated by NF-κB inducers. Inhibition of NF-κB prevented the up-regulation of β-arrestin-1 mRNA, whereas activation of NF-κB led to increased β-arrestin-1 expression. β-Arrestin-1 promoter activity was consistently enhanced upon NF-κB activation as a result of the presence of a highly conserved κB site. β-Arrestin-1, in turn, suppressed the transcriptional activity of NF-κB by interfering with the interaction between p65 and p50. β-Arrestin-1-deficient mice displayed reduced TNF-α-induced cell death and increased expression of antiapoptotic genes. Reintroduction of β-arrestin-1, but not its mutant, which is unable to interfere with the p65-p50 interaction, into β-arrestin-deficient mouse embryonic fibroblasts partially restored sensitivity to TNF-α-induced cell death. These findings reveal NF-κB and β-arrestin-1 to be key components of a negative feedback circuit that is necessary to regulate cell death.-Li, J., Guo, A., Wang, Q., Li, Y., Zhao, J., Lu, J., Pei, G. NF-κB directly regulates β-arrestin-1 expression and forms a negative feedback circuit in TNF-α-induced cell death.

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Nonhematopoietic β-Arrestin-1 Inhibits Inflammation in a Murine Model of Polymicrobial Sepsis

Cited by 15 publications

References 51 publications

Multifaceted role of β-arrestins in inflammation and disease

Multifaceted role of β-arrestins in inflammation and disease

Inflammatory cytokine expression in patients with sepsis at an intensive care unit

NF‐κB directly regulates β‐arrestin‐1 expression and forms a negative feedback circuit in TNF‐α‐induced cell death

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