Human Neuronal Cells Possess Functional Cytoplasmic and TLR-Mediated Innate Immune Pathways Influenced by Phosphatidylinositol-3 Kinase Signaling

Peltier, Daniel; Simms, Allison; Farmer, Jocelyn R.; Miller, David J.

doi:10.4049/jimmunol.0904133

Cited by 73 publications

(100 citation statements)

References 80 publications

(117 reference statements)

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“…Another possibility is that TLRs might induce post-SCI NLRP1 inflammasome formation. Although TLRs are generally considered to be expressed in microglia and astrocytes, recent research has showed that TLR expression in neurons is pivotal under both physiological and pathological conditions [54][55][56][57]. Perhaps SCI changes expression of certain TLRs which recognize danger signals after injury and subsequently causes inflammasome formation.…”

Section: Discussionmentioning

confidence: 99%

Heme Oxygenase-1 Promotes Neuron Survival through Down-Regulation of Neuronal NLRP1 Expression after Spinal Cord Injury

Lin

Wang

2017

The Spine Journal

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Section: Discussionmentioning

confidence: 99%

Heme Oxygenase-1 Promotes Neuron Survival through Down-Regulation of Neuronal NLRP1 Expression after Spinal Cord Injury

Lin

Wang

2017

The Spine Journal

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“…The TC-83 vaccine strain of VEEV was obtained from Robert Tesh (University of Texas Medical Branch, Galveston, TX), and the New Guinea C and H241 strains of DENV-2 and DENV-4, respectively, were obtained from Sonja Gerrard (University of Michigan, Ann Arbor, MI). Green fluorescent protein (GFP)-tagged Sendai virus (GFP-SeV) was obtained from Valery Grdzelishvili (University of North Carolina at Charlotte, Charlotte, NC) and has been previously described (24).…”

Section: Methodsmentioning

confidence: 99%

“…WEEV replicon assays used BSR-T7 cells and pWR-LUC, pW-nsP, or pWR-⌬LUC and measured fLUC accumulation as a surrogate marker for viral RNA replication as previously described (13,19). GFP-SeV replication was determined by fluorescence accumulation as previously described (24). Quantitative reverse-transcription (RT)-PCR was done as previously described (19,24,25), where threshold cycle (⌬⌬C T ) values were calculated to determine relative RNA levels.…”

Section: Methodsmentioning

confidence: 99%

“…GFP-SeV replication was determined by fluorescence accumulation as previously described (24). Quantitative reverse-transcription (RT)-PCR was done as previously described (19,24,25), where threshold cycle (⌬⌬C T ) values were calculated to determine relative RNA levels. The sequences for the 18S rRNA and WEEV envelope glycoprotein 1 primers have been previously published (25).…”

Section: Methodsmentioning

confidence: 99%

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Novel Indole-2-Carboxamide Compounds Are Potent Broad-Spectrum Antivirals Active against Western Equine Encephalitis Virus In Vivo

Delekta

Dobry

Sindac

et al. 2014

J Virol

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“…The PRRs are abundantly expressed in both neuronal and non-neuronal cells including the immune cells (e.g. monocytes, macrophages, dendritic cells and other immunerelated cells such as keratinocytes) (82,83). Other types of PRRs include RIG-like helicases (RLHs), C-type lectins (CTLs) and the recently discovered, Nod-like receptors (NLRs) (84).…”

Section: Intracellular Signals In Inflammationmentioning

confidence: 99%

The immunomodulation of dynorphin 1-17 and its biotransformation fragments on inflammatory signalling pathways

Rahiman¹,

Sarah²

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Inflammation is a complex physiological process that involves host defense mechanisms in response to the intrusion of harmful external stimuli. Uncoordinated inflammatory responses, however, are the underlying pathophysiological cause of many chronic diseases. Inflammation is characterised by the burgeoning migration of leukocytes to the point of injury and subsequent release of pro-nociceptive mediators, generating inflammatory pain. Dynorphin 1-17 (DYN 1-17) is endogenously produced and released from leukocytes upon stimulation by local inflammatory factors in the inflamed area. This opioid peptide primarily binds to kappa-opioid receptor (KOR) to produce analgesia. Under inflammatory milieu, DYN 1-17 undergoes spontaneous degradation, yielding a variety of opioid and non-opioid fragments that may have significant implications in inflammation. The underlying cellular effects of these fragments remain unclear. This thesis seeks to explore potential mechanistic insights into selected major DYN 1-17 fragments, identified from a previous biotransformation study of DYN 1-17 in rodent inflamed tissue. This thesis examines the DYN 1-17 fragments modulation of intracellular signals associated with inflammation and thereby, gain an insight into novel therapeutic targets through exploring these endogenous mechanisms.Utilising THP-1 macrophages as an in vitro model of inflammation, this thesis begins with a semiquantitative assessment of nuclear factor-kappa B/p65 (NF-κB/p65) translocation, a major transcription factor that regulates genes responsible for immune and inflammatory responses. The findings presented in Chapter Three of this thesis demonstrated that DYN 1-17 and selected major fragments (DYN 1-6, 1-7, 1-9, 1-10, 1-11, 3-14, 6-12, 2-17 and 7-17) significantly attenuated NF-κB/p65 nuclear translocation induced by lipopolysaccharide (LPS), with the greatest reduction observed with DYN 1-7 at 10 nM. A selective KOR antagonist, ML-190, was used to examine KOR involvement in this inhibitory action. ML-190 significantly reversed the inhibition of NF-κB/p65 translocation produced by DYN 1-17, DYN 1-6, DYN 1-7 and DYN 1-9, but not DYN 1-10 and DYN 1-11.Cytokine production is linked as a downstream process to NF-κB activation; hence it is necessary to evaluate the ability of DYN 1-17 and selected biotransformation fragments in the modulation of IL-1β and TNF-α release in differentiated THP-1 cells, as presented in Chapter Four, to gain an insight into the effects on major pro-inflammatory cytokines. DYN 1-17 and the fragments, demonstrated differential modulatory effects on LPS-induced release of IL-1β and TNF-α. DYN 1-7 and DYN 1-6, inhibited and elevated the secretion of both cytokines, respectively, in a concentration-dependent manner (10 -11 to 10 -7 M). DYN 1-17, however, only inhibited IL-1β release from differentiated iii THP-1 cells and had no effect on TNF-α secretion. Intriguingly, DYN 3-14 at 10 -17 to 10 -11 M demonstrated significant inhibition on IL-1β release and paradoxically increased TNF-α lev...

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Human Neuronal Cells Possess Functional Cytoplasmic and TLR-Mediated Innate Immune Pathways Influenced by Phosphatidylinositol-3 Kinase Signaling

Abstract: Material

Cited by 73 publications

References 80 publications

Heme Oxygenase-1 Promotes Neuron Survival through Down-Regulation of Neuronal NLRP1 Expression after Spinal Cord Injury

Heme Oxygenase-1 Promotes Neuron Survival through Down-Regulation of Neuronal NLRP1 Expression after Spinal Cord Injury

Novel Indole-2-Carboxamide Compounds Are Potent Broad-Spectrum Antivirals Active against Western Equine Encephalitis Virus In Vivo

The immunomodulation of dynorphin 1-17 and its biotransformation fragments on inflammatory signalling pathways

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