Exposure to environmental black carbon exacerbates nasal epithelial inflammation via the reactive oxygen species (ROS)–nucleotide‐binding, oligomerization domain–like receptor family, pyrin domain containing 3 (NLRP3)–caspase‐1–interleukin 1β (IL‐1β) pathway

2020 ◽  
Author(s):  
Ying Li ◽  
Yuhui Ouyang ◽  
Jian Jiao ◽  
Zhaojun Xu ◽  
Luo Zhang
Keyword(s):  
Reactive Oxygen Species ◽  
Black Carbon ◽  
Nucleotide Binding ◽  
Interleukin 1Β ◽  
Oxygen Species ◽  
Caspase 1 ◽  
Pyrin Domain ◽  
Epithelial Inflammation ◽  
Receptor Family ◽  
Oligomerization Domain

scholarly journals The Inflammasome and Caspase-1 Activation: A New Mechanism Underlying Increased Inflammatory Activity in Human Visceral Adipose Tissue

Endocrinology ◽  
2011 ◽  
Vol 152 (10) ◽  
pp. 3769-3778 ◽  
Author(s):  
Tim B. Koenen ◽  
Rinke Stienstra ◽  
Lambertus J. van Tits ◽  
Leo A. B. Joosten ◽  
Jeroen F. van Velzen ◽  
...  
Keyword(s):  
T Cells ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Cd8 T Cells ◽  
Nucleotide Binding ◽  
Caspase 1 ◽  
Pyrin Domain ◽  
Inflammatory Status ◽  
Visceral Adipose ◽  
Oligomerization Domain

The immune competent abdominal adipose tissue, either stored viscerally [visceral adipose tissue (VAT)] or sc [sc adipose tissue (SAT)], has been identified as a source of IL-1β and IL-18. To become active, the proforms of these cytokines require processing by caspase-1, which itself is mediated by the inflammasome. In this descriptive study, we investigate the expression of inflammasome components and caspase-1 in human fat and determine whether caspase-1 activity contributes to the enhanced inflammatory status of VAT. Paired SAT and VAT biopsies from 10 overweight subjects (body mass index, 25–28 kg/m2) were used to study the cellular composition and the intrinsic inflammatory capacity of both adipose tissue depots. The percentage of CD8+ T cells within the lymphocyte fraction was significantly higher in VAT compared with SAT (41.6 vs. 30.4%; P < 0.05). Adipose tissue cultures showed a higher release of IL-1β (10-fold; P < 0.05), IL-18 (3-fold; P < 0.05), and IL-6 and IL-8 (3-fold, P < 0.05; and 4-fold, P < 0.05, respectively) from VAT compared with SAT that was significantly reduced by inhibiting caspase-1 activity. In addition, caspase-1 activity was 3-fold (P < 0.05) higher in VAT compared with SAT, together with an increase in the protein levels of the inflammasome members apoptosis-associated speck-like protein containing a C-terminal caspase-recruitment domain (2-fold; P < 0.05) and nucleotide-binding oligomerization domain- like receptor pyrin domain containing 3 (2-fold; nonsignificant). Finally, caspase-1 activity levels were positively correlated with the percentage of CD8+ T cells present in adipose tissue. Our results show that caspase-1 and nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 inflammasome members are abundantly present in human VAT. The increased intrinsic caspase-1 activity in VAT represents a novel and specific inflammatory pathway that may determine the proinflammatory character of this specific depot.

scholarly journals Absence of the NOD2 protein renders epithelia more susceptible to barrier dysfunction due to mitochondrial dysfunction

2017 ◽  
Vol 313 (1) ◽  
pp. G26-G38 ◽  
Author(s):  
Alpana Saxena ◽  
Fernando Lopes ◽  
Karen K. H. Poon ◽  
Derek M. McKay
Keyword(s):  
Reactive Oxygen Species ◽  
Barrier Function ◽  
Paneth Cell ◽  
Metabolic Stress ◽  
Reactive Oxygen ◽  
Nucleotide Binding ◽  
Intracellular Bacteria ◽  
Oxygen Species ◽  
E Coli ◽  
Oligomerization Domain

Irregular mitochondria structure and reduced ATP in some patients with IBD suggest that metabolic stress contributes to disease. Loss-of-function mutation in the nucleotide-binding oligomerization domain (NOD)-2 gene is a major susceptibility trait for IBD. Hence, we assessed if loss of NOD2 further impairs the epithelial barrier function instigated by disruption of mitochondrial ATP synthesis via the hydrogen ionophore dinitrophenol (DNP). NOD2 protein (virtually undetectable in epithelia under basal conditions) was increased in T84 (human colon cell line) cells treated with noninvasive Escherichia coli + DNP (16 h). Increased intracellular bacteria in wild-type (WT) and NOD2 knockdown (KD) cells and colonoids from NOD2−/− mice were mediated by reactive oxygen species (ROS) and the MAPK ERK1/2 pathways as determined by cotreatment with the antioxidant mitoTEMPO and the ERK inhibitor U0126: ROS was upstream of ERK1/2 activation. Despite increased E. coli in DNP-treated NOD2 KD compared with WT cells, there were no differences in the internalization of fluorescent inert beads or dead E. coli particles. This suggests that lack of killing in the NOD2 KD cells was responsible for the increased numbers of viable intracellular bacteria; a conclusion supported by evidence of reduced autophagy in NOD2 KD T84 epithelia. Thus, in a two-hit hypothesis, decreased barrier function due to dysfunctional mitochondrial is amplified by lack of NOD2 in transporting enterocytes: subsequently, greater numbers of bacteria entering the mucosa would be a significant inflammatory threat especially since individuals with NOD2 mutations have compromised macrophage and Paneth cell responses to bacteria. NEW & NOTEWORTHY Increased internalization of bacteria by epithelia with dysfunctional mitochondria (reduced ATP) is potentiated if the cells lack nucleotide-binding oligomerization domain 2 (NOD2), mutations in which are inflammatory bowel disease-susceptibility traits. Uptake of bacteria was dependent on reactive oxygen species and MAP-kinase activity, and the increased viable intracellular bacteria in NOD2−/− cells likely reflect a reduced ability to recognize and kill bacteria. Thus a significant barrier defect occurs with NOD2 deficiency in conjunction with metabolic stress that could contribute to inflammation.

scholarly journals Blue Light Induces Impaired Autophagy through Nucleotide-Binding Oligomerization Domain 2 Activation on the Mouse Ocular Surface

2021 ◽  
Vol 22 (4) ◽  
pp. 2015
Author(s):  
Ying Li ◽  
Rujun Jin ◽  
Lan Li ◽  
Ji Suk Choi ◽  
Jonghwa Kim ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Blue Light ◽  
Ocular Surface ◽  
Light Exposure ◽  
Reactive Oxygen ◽  
Nucleotide Binding ◽  
Oxygen Species ◽  
Knock Out ◽  
Corneal Epithelial ◽  
Oligomerization Domain

In this study, we investigated the effects of blue light exposure on nucleotide-binding oligomerization domain 2 (NOD2) expression on the mouse ocular surface and evaluated the role of NOD2 activation in light-induced cell death. Mice were divided into wild-type (WT), NOD2-knock out (KO), WT + blue light (WT + BL), and NOD2-KO + blue light (NOD2-KO + BL) groups, and the mice in the WT+BL and NOD2-KO + BL groups were exposed to blue light for 10 days. After 10 days of blue light exposure, increased reactive oxygen species and malondialdehyde were observed in the WT + BL and NOD2-KO + BL groups, and the WT + BL group showed a higher expression of NOD2 and autophagy related 16 like 1. Although both WT+BL and NOD2-KO + BL groups showed an increase in the expression of light chain 3-II, NOD2-KO + BL mice had a significantly lower p62 expression than WT + BL mice. In addition, NOD2-KO+BL mice had significantly lower corneal epithelial damage and apoptosis than WT + BL mice. In conclusion, blue light exposure can induce impaired autophagy by activation of NOD2 on the ocular surface. In addition, the reactive oxygen species (ROS)–NOD2–autophagy related 16 like 1 (ATG16L) signaling pathway may be involved in the blue-light-induced autophagy responses, resulting in corneal epithelial apoptosis.

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