Characterization of the Pro‐Inflammatory Cytokine IL‐1β on Butyrate Oxidation in Colorectal Cancer Cells

Johnstone, Megan; Bennett, Natalie E.; Standifer, Cynthia; Smith, Alexis D.; Han, Anna; Bettaieb, Ahmed; Whelan, Jay; Donohoe, Dallas R.

doi:10.1002/jcb.25824

Cited by 20 publications

(17 citation statements)

References 39 publications

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“…Previous studies demonstrated that mutations in the IL-6 gene may increase the risk for AD [45,46]. IL-1β activates NF-κB and p38 signaling pathways to further worsen neuronal cell dysfunction [47]. Therefore, inhibiting the expression of RAGE and RAGE/NF-κB mediated neuroinflammatory responses may be an effective therapeutic strategy for AD.…”

Section: Discussionmentioning

confidence: 99%

Tanshinone IIA attenuates neuroinflammation via inhibiting RAGE/NF-κB signaling pathway in vivo and in vitro

Ding

Lin

Liu

et al. 2020

J Neuroinflammation

101

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Background Glial activation and neuroinflammation play a crucial role in the pathogenesis and development of Alzheimer’s disease (AD). The receptor for advanced glycation end products (RAGE)-mediated signaling pathway is related to amyloid beta (Aβ)-induced neuroinflammation. This study aimed to investigate the neuroprotective effects of tanshinone IIA (tan IIA), a natural product isolated from traditional Chinese herbal Salvia miltiorrhiza Bunge, against Aβ-induced neuroinflammation, cognitive impairment, and neurotoxicity as well as the underlying mechanisms in vivo and in vitro. Methods Open-field test, Y-maze test, and Morris water maze test were conducted to assess the cognitive function in APP/PS1 mice. Immunohistochemistry, immunofluorescence, thioflavin S (Th-S) staining, enzyme-linked immunosorbent assay (ELISA), real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and western blotting were performed to explore Aβ deposition, synaptic and neuronal loss, microglial and astrocytic activation, RAGE-dependent signaling, and the production of pro-inflammatory cytokines in APP/PS1 mice and cultured BV2 and U87 cells. Results Tan IIA treatment prevented spatial learning and memory deficits in APP/PS1 mice. Additionally, tan IIA attenuated Aβ accumulation, synapse-associated proteins (Syn and PSD-95) and neuronal loss, as well as peri-plaque microgliosis and astrocytosis in the cortex and hippocampus of APP/PS1 mice. Furthermore, tan IIA significantly suppressed RAGE/nuclear factor-κB (NF-κB) signaling pathway and the production of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in APP/PS1 mice and cultured BV2 and U87 cells. Conclusions Taken together, the present results indicated that tan IIA improves cognitive decline and neuroinflammation partly via inhibiting RAGE/NF-κB signaling pathway in vivo and in vitro. Thus, tan IIA might be a promising therapeutic drug for halting and preventing AD progression.

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Section: Discussionmentioning

confidence: 99%

Tanshinone IIA attenuates neuroinflammation via inhibiting RAGE/NF-κB signaling pathway in vivo and in vitro

Ding

Lin

Liu

et al. 2020

J Neuroinflammation

101

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“…Tumor-promoting inflammation is now an emerging hallmark of cancer, which sounds unanticipated and paradoxical but proved to be virtual in its tumorigenesis journey. Succinate is widely accepted as an inflammatory signal and induces interleukin-1β (IL-1β) through HIF-1α [ 89 ] while IL-1β has been demonstrated to be elevated in colorectal cancer [ 90 ], oral cancer [ 91 ] and colon cancer [ 92 ]. Taken together, accumulation of succinate in the tumor microenvironment finally enhances the tumor-associated inflammation.…”

Section: Introductionmentioning

confidence: 99%

Succinate: An initiator in tumorigenesis and progression

Zhao

Qin

2017

Oncotarget

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As an intermediate metabolite of the tricarboxylic acid cycle in mitochondria, succinate is widely investigated for its role in metabolism. In recent years, an increasing number of studies have concentrated on the unanticipated role of succinate outside metabolism, acting as, for instance, an inflammatory signal or a carcinogenic initiator. Actually, succinate dehydrogenase gene mutations and abnormal succinate accumulation have been observed in a battery of hereditary and sporadic malignancies. In this review, we discuss the unexpected role of succinate and possible mechanisms that may contribute to its accumulation. Additionally, we describe how the high concentration of succinate in the tumor microenvironment acts as an active participant in tumorigenesis, rather than a passive bystander or innocent victim. Focusing on mechanism-based research, we summarize some targeted therapies which have been applied to the clinic or are currently under development. Furthermore, we posit that investigational drugs with different molecular targets may expand our horizon in anticancer therapy.

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“…Several groups over the last two decades have also observed elevated inflammatory cytokine and chemokine profiles in the serum of patients with solid cancers. Significantly elevated expression of IL1-β, IL-6, IL-8, IL-10, IL-17, TNF-α, TGF-β, IFNγ, and C-X-C motif chemokine ligand 1 (CXCL1) has been seen in colorectal cancer and other solid cancers like lung cancer (51)(52)(53)(54)(55).…”

Section: Discussionmentioning

confidence: 99%

KMP01D Demonstrates Beneficial Anti-inflammatory Effects on Immune Cells: An ex vivo Preclinical Study of Patients With Colorectal Cancer

et al. 2020

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Background: Colorectal cancer (CRC) is frequently associated with dysbiosis of the gut microbiome which, together with a compromised gut barrier, can result in perioperative endotoxin leakage into the circulation. Constant local and systemic inflammatory activity is suggested to facilitate metastases formation. Previous studies have pointed to the capacity of a colostrum preparation to neutralize endotoxins within the gastrointestinal tract which could ameliorate associated inflammatory responses and tumor recurrence in affected patients. This study aimed to examine the effects of the colostrum preparation, KMP01D, on the inflammatory activity of patient-derived immune cells.Methods: The effects of KMP01D on pro-/anti-inflammatory cytokine responses and apoptosis were examined ex vivo using immune cells from CRC patients (stages I-IV, n = 48). The expression of CD14, CD68, Toll-like receptor (TLR)4, and insulin-like growth factor (IGF)-1 was also analyzed.Results: KMP01D increased interleukin (IL)-10 and IL-13 anti-inflammatory cytokine expression in patient-derived peripheral blood mononuclear cells (PBMCs). Interestingly, KMP01D also decreased the secretion of IL-1β, IL-6, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-12 inflammatory cytokines, and IGF-1 in these cells. Moreover, CD14 and TLR4 expression involved in endotoxin signaling was downregulated in PBMCs and tumor-derived cells. Apoptosis of immune cells and tumor-derived cells was likewise enhanced with KMP01D. Addition of vitamin D3 as a cofactor demonstrated enhanced anti-inflammatory effects.Conclusions: KMP01D demonstrated beneficial ex vivo effects on inflammatory cytokine responses in PBMCs and enhanced apoptosis of immune cells from CRC patients. In line with previous clinical trials, we present new evidence endorsing KMP01D as a treatment strategy to regulate stage-dependent local and systemic inflammation in CRC patients.

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Characterization of the Pro‐Inflammatory Cytokine IL‐1β on Butyrate Oxidation in Colorectal Cancer Cells

Cited by 20 publications

References 39 publications

Tanshinone IIA attenuates neuroinflammation via inhibiting RAGE/NF-κB signaling pathway in vivo and in vitro

Tanshinone IIA attenuates neuroinflammation via inhibiting RAGE/NF-κB signaling pathway in vivo and in vitro

Succinate: An initiator in tumorigenesis and progression

KMP01D Demonstrates Beneficial Anti-inflammatory Effects on Immune Cells: An ex vivo Preclinical Study of Patients With Colorectal Cancer

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