Nitric Oxide Engages an Anti-inflammatory Feedback Loop Mediated by Peroxiredoxin 5 in Phagocytes

Graham, Daniel B.; Jasso, Guadalupe J.; Mok, Amanda; Goel, Gautam; Ng, Aylwin; Kolde, Raivo; Varma, Mukund; Doench, John G.; Root, David E.; Clish, Clary B.; Carr, Steven A.; Xavier, Ramnik J.

doi:10.1016/j.celrep.2018.06.081

Cited by 31 publications

(13 citation statements)

References 80 publications

(96 reference statements)

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“…Here, we found that NO levels were decreased in the hemolymph of bay scallops treated with low and medium concentrations of TD 49 at 6 and 12 hpe, as well as for the high concentration at 6 hpe. The phenomenon might be due to the elevated PrxV expression, since it was demonstrated that the antioxidant response, dependent on PrxV, acts as a negative feedback loop to suppress NO production [24]. Although the level of NO recovered to control levels at 48 hpe, NO modulation caused by TD 49 exposure might disturb a variety of immune homeostatic and other physiological processes.…”

Section: Discussionmentioning

confidence: 99%

Effect of the Algicide Thiazolidinedione 49 on Immune Responses of Bay Scallop Argopecten Irradians

Chi

Yun²,

Giri³

et al. 2019

Molecules

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The thiazolidinedione 49 (TD49) is an effective algaecide against harmful algae; however, its potential effects on the immune function of the edible bay scallop are unclear. Therefore, the present work studied the effects of TD49 on the immune response in bay scallop by evaluating activities of acid phosphatase (ACP), alkaline phosphatase (ALP), and superoxide dismutase (SOD), as well as nitric oxide (NO) levels, total protein content, and expression of immune genes (CTL-6, PGRP, PrxV, MT, and Cu/Zn-SOD) at 3–48 h post-exposure (hpe) to TD49. The activities of ACP and ALP significantly increased in TD49-treated groups at 3–24 hpe, whereas NO levels decreased significantly in 0.58 and 0.68 μM of TD49 at 6–24 hpe, after which the level was similar to that in the untreated control. Moreover, SOD activity significantly increased in all three concentration groups at 3–6 hpe, while it decreased at 12 hpe in the 0.68 μM TD49 treatment group. Notably, total protein content increased with TD49 treatment at each time interval. The results revealed that variable effects on the expression of immune-related genes were observed after treatment with TD49. The findings demonstrate that exposure of scallops to TD49 changes immune responses and expression of immune-related genes. We hypothesize that TD49 may disrupt immune system in bay scallop. The current investigation highlights the potential negative effects of using TD49 as an algaecide on marine economic bivalves to control harmful algal blooms in marine environments.

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Section: Discussionmentioning

confidence: 99%

Effect of the Algicide Thiazolidinedione 49 on Immune Responses of Bay Scallop Argopecten Irradians

Chi

Yun²,

Giri³

et al. 2019

Molecules

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“…In order to delineate how the inflammatory response may impact fibroblast phenotypes, we compared the expression profiles of cells between water-and DSS-treated samples accounting for different levels of the lineage tree: (1) the broader lineage; and ( 2 ), suggesting that fibroblasts exhibit a metabolic adaptation to counterbalance oxidative stress associated with inflammation [65]. Notably, the antioxidant system appears to be a critical player in fibrosis development, which is prevalent across many pathological conditions [66][67][68][69], thereby suggesting that fibroblast activation in colitis may be linked, at least in part, to this process.…”

Section: Intestinal Inflammation Elicits a Dynamic Fibroblast Responsementioning

confidence: 99%

Colon stroma mediates an inflammation-driven fibroblastic response controlling matrix remodeling and healing

et al. 2022

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Chronic inflammation is often associated with the development of tissue fibrosis, but how mesenchymal cell responses dictate pathological fibrosis versus resolution and healing remains unclear. Defining stromal heterogeneity and identifying molecular circuits driving extracellular matrix deposition and remodeling stands to illuminate the relationship between inflammation, fibrosis, and healing. We performed single-cell RNA-sequencing of colon-derived stromal cells and identified distinct classes of fibroblasts with gene signatures that are differentially regulated by chronic inflammation, including IL-11–producing inflammatory fibroblasts. We further identify a transcriptional program associated with trans-differentiation of mucosa-associated fibroblasts and define a functional gene signature associated with matrix deposition and remodeling in the inflamed colon. Our analysis supports a critical role for the metalloprotease Adamdec1 at the interface between tissue remodeling and healing during colitis, demonstrating its requirement for colon epithelial integrity. These findings provide mechanistic insight into how inflammation perturbs stromal cell behaviors to drive fibroblastic responses controlling mucosal matrix remodeling and healing.

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“…In particular, PrdxV among peroxiredoxin isotypes is a peroxynitrite reductase with a high rate constant for peroxinitrite, (7 ± 3) × 10 7 M −1 s −1 21 . Recently, it has been reported that PrdxV acts as a negative feedback loop suppressing NO production 22 . Thus, we wondered whether there was an association with oxidative stress in promoting the progression of UUO-induced renal fibrosis in the kidney of PrdxV si mice.…”

Section: Resultsmentioning

confidence: 99%

Peroxiredoxin V (PrdxV) negatively regulates EGFR/Stat3-mediated fibrogenesis via a Cys48-dependent interaction between PrdxV and Stat3

Choi

Kim

et al. 2019

Sci Rep

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Activation of the epidermal growth factor receptor (EGFR)/signal transducer and activator of transcription 3 (Stat3) signaling pathway has been reported to be associated with renal fibrosis. We have recently demonstrated that peroxiredoxin V (PrdxV) acted as an antifibrotic effector by inhibiting the activity of Stat3 in TGF-β-treated NRK49F cells. However, the underlying mechanism of PrdxV remains poorly understood. To investigate molecular mechanism of PrdxV, we used a transgenic mouse model expressing PrdxV siRNA (PrdxV si mice) and performed unilateral ureteral obstruction (UUO) for 7 days. 209/MDCT cells were transiently transfected with HA-tagged WT PrdxV and C48S PrdxV. Transgenic PrdxV si mice displayed an exacerbated epithelial-to-mesenchymal transition (EMT) as well as an increase in oxidative stress induced by UUO. In the UUO kidney of the PrdxV si mouse, knockdown of PrdxV increased Tyr1068-specific EGFR and Stat3 phosphorylation, whereas overexpression of WT PrdxV in 209/MDCT cells showed the opposite results. Immunoprecipitation revealed the specific interaction between WT PrdxV and Stat3 in the absence or presence of TGF-β stimulation, whereas no PrdxV-EGFR or C48S PrdxV-Stat3 interactions were detected under any conditions. In conclusion, PrdxV is an antifibrotic effector that sustains renal physiology. Direct interaction between PrdxV and Stat3 through Cys48 is a major molecular mechanism.

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Nitric Oxide Engages an Anti-inflammatory Feedback Loop Mediated by Peroxiredoxin 5 in Phagocytes

Cited by 31 publications

References 80 publications

Effect of the Algicide Thiazolidinedione 49 on Immune Responses of Bay Scallop Argopecten Irradians

Effect of the Algicide Thiazolidinedione 49 on Immune Responses of Bay Scallop Argopecten Irradians

Colon stroma mediates an inflammation-driven fibroblastic response controlling matrix remodeling and healing

Peroxiredoxin V (PrdxV) negatively regulates EGFR/Stat3-mediated fibrogenesis via a Cys48-dependent interaction between PrdxV and Stat3

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