Serotonin disturbs colon epithelial tolerance of commensal E. coli by increasing NOX2-derived superoxide

Banskota, Suhrid; Regmi, Sushil Chandra; Gautam, Jaya; Gurung, Pallavi; Lee, Yujeong; Ku, Sae Kwang; Lee, Jin-Hyung; Lee, Jintae; Chang, Hyeun Wook; Park, Sang Joon; Kim, Jung-Ae

doi:10.1016/j.freeradbiomed.2017.02.034

Cited by 35 publications

(30 citation statements)

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“…In an effort to identify the underlying mechanisms by which serotonin induced cell inflammation and apoptosis in corneal epithelial cells, we reviewed the related literature and found that the NF-jB pathway was closely related to serotonin and had regulatory effects on cell inflammation and apoptosis. 14 Interestingly, we found that the p65 phosphorylation level (a subunit of NF-jB) was significantly increased, with a significant decrease in IjBa protein abundance, with serotonin treatment (P < 0.01) (Figs. 6A, 6B).…”

Section: Serotonin Induces Cell Inflammation and Apoptosis By Activatmentioning

confidence: 79%

“…Accumulating evidence has confirmed that prolonged SSRI use can activate the peripheral TLR4 signal pathway and NF-jB signaling. 13,14 TLR4 is a transmembrane protein receptor that is involved in innate immunity. TLR4 signaling can activate many inflammatory cytokines that have been proven to be triggers of DED.…”

mentioning

confidence: 99%

“…15 5-HT binding to 5-HTRs can activate NF-jB. 14 As a transcriptional activator, NF-jB increases the expression levels of downstream genes, including the inflammatory cytokine genes TNFa and TLR4 and the apoptosis-related genes AIF and BAX, and provokes a rapid inflammatory response and cell apoptosis. 14,16,17 However, the mechanism by which SSRIs induce DED is not clear.…”

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confidence: 99%

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Selective Serotonin Reuptake Inhibitors Aggravate Depression-Associated Dry Eye Via Activating the NF-κB Pathway

Zhang

Yin

Yue

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Our study aimed to evaluate the side effects of selective serotonin reuptake inhibitors (SSRIs) on the ocular surface. METHODS. Twenty patients with depression and dry eye disease (DED) were randomly picked to receive SSRI treatment, whereas another 20 patients received placebo treatment. The serotonin, inflammatory cytokine, and proapoptotic protein levels were determined by using protein chip, qRT-PCR, and ELISA analyses. A rat depression model was established, and SSRIs were applied for 3 or 6 weeks. Tear production and corneal epithelial barrier function were evaluated. The serotonin and inflammatory cytokine levels were analyzed by qRT-PCR, immunohistochemical staining, and ELISA. Human corneal epithelial cells were subjected to serotonin, a HTR antagonist, and/or an NF-jB signaling inhibitor. The inflammatory cytokine and proapoptotic protein levels were determined by qRT-PCR, Western blot analysis, and ELISA. The cell apoptosis rate was assessed by using flow cytometry. RESULTS. The SSRI group had higher tear serotonin levels and more serious inflammation and cell apoptosis on the ocular surface. In the rat depression model, depression decreased tear secretion and increased IL-1b and TNF-a production, whereas the serotonin, TLR2, and TLR4 levels were not increased. SSRI aggravated DED, disrupted the corneal epithelial barrier, and promoted an inflammatory response on the ocular surface by increasing the tear serotonin levels. In addition, serotonin induced an inflammatory response and cell apoptosis in corneal epithelial cells by activating NF-jB signaling. CONCLUSIONS. SSRIs aggravate depression-associated DED via activating the NF-jB pathway. The antagonist of HTRs or the inhibitor of NF-jB signaling presents a potential therapeutic strategy for depression-associated DED. (Trial registration number, ChiCTR1800015592).

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Section: Serotonin Induces Cell Inflammation and Apoptosis By Activatmentioning

confidence: 79%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Selective Serotonin Reuptake Inhibitors Aggravate Depression-Associated Dry Eye Via Activating the NF-κB Pathway

Zhang

Yin

Yue

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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“…A lucigenin chemiluminescence assay was performed following a previously published method (Banskota et al ., ). Briefly, cells were seeded in white 96‐well plates at a density of 5 × 10 4 cells per well and treated with 4‐HNE, niacin or 3‐OHBA in assay buffer (pH 7.4) containing 130 mM NaCl, 5 mM KCl, 1 mM MgCl 2 , 1.5 mM CaCl 2 , 35 mM phosphoric acid and 20 mM HEPES in the absence or presence of SOD for an indicated time period.…”

Section: Methodsmentioning

confidence: 97%

4‐Hydroxynonenal‐induced GPR109A (HCA₂ receptor) activation elicits bipolar responses, G_αi‐mediated anti‐inflammatory effects and G_βγ‐mediated cell death

Gautam

Banskota

Shah

et al. 2018

British J Pharmacology

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“…For instance, NADPH oxidase activation is essential for antigen presentation in B cells, T cell receptor stimulation and subset polarization . In addition, Nox2 has also been detected in colonic epithelial cells where its capacity to produce superoxide (O 2 − ) in response to microbial stimulations may facilitate the attachment of commensals such as Escherichia coli to the colonic mucus layer . Epithelial cell‐derived O 2 − within the gut has been implicated to modulate the composition of the gut microbiome, by altering gene transcription and crosstalk between bacteria.…”

Section: Introductionmentioning

confidence: 99%

The roles of NADPH oxidase in modulating neutrophil effector responses

Zeng

Miralda

Armstrong

et al. 2019

Molecular Oral Microbiology

105

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Reactive oxygen species (ROS) collectively refer to a large group of highly reactive derivatives of oxygen generated as a consequence of metabolic processes or during host stress response. Although associated with oxidative damage, when produced at low regulated levels, oxidants are essential for redox modulation of cellular pathways, immune effector function, cell signaling and anti-microbial responses.The majority of ROS generated in a cell is by the activation of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidases or NOX enzyme complexes. NOX enzyme family members NOX1, NOX2, NOX3, NOX4, NOX5 and the dual oxidase (DUOX) enzymes DUOX1, and DUOX2 are membrane associated hetero-oligomeric complexes that are dedicated to generation of ROS by using oxygen as its substrate. NOX enzymes are expressed in a cell specific or tissue specific manner and are rapidly activated in response to external stressors to generate large amounts of ROS. NOX2 or gp91 phox is the main catalytic subunit of the leukocyte NADPH oxidase complex. It is highly expressed in phagocytes (neutrophils, monocytes, macrophages, dendritic cells) and at much lower levels in lymphocytes, endothelial cells and colonic epithelial cells. 1,2 NOX2 derived oxidants modulate multiple cellular processes independent of their anti-microbial function. For instance, NADPH oxidase activation is essential for antigen presentation in B cells 3 , T cell receptor stimulation 4

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Serotonin disturbs colon epithelial tolerance of commensal E. coli by increasing NOX2-derived superoxide

Cited by 35 publications

References 42 publications

Selective Serotonin Reuptake Inhibitors Aggravate Depression-Associated Dry Eye Via Activating the NF-κB Pathway

Selective Serotonin Reuptake Inhibitors Aggravate Depression-Associated Dry Eye Via Activating the NF-κB Pathway

4‐Hydroxynonenal‐induced GPR109A (HCA₂ receptor) activation elicits bipolar responses, G_αi‐mediated anti‐inflammatory effects and G_βγ‐mediated cell death

The roles of NADPH oxidase in modulating neutrophil effector responses

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Serotonin disturbs colon epithelial tolerance of commensal E. coli by increasing NOX2-derived superoxide

Cited by 35 publications

References 42 publications

Selective Serotonin Reuptake Inhibitors Aggravate Depression-Associated Dry Eye Via Activating the NF-κB Pathway

Selective Serotonin Reuptake Inhibitors Aggravate Depression-Associated Dry Eye Via Activating the NF-κB Pathway

4‐Hydroxynonenal‐induced GPR109A (HCA2 receptor) activation elicits bipolar responses, Gαi‐mediated anti‐inflammatory effects and Gβγ‐mediated cell death

The roles of NADPH oxidase in modulating neutrophil effector responses

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4‐Hydroxynonenal‐induced GPR109A (HCA₂ receptor) activation elicits bipolar responses, G_αi‐mediated anti‐inflammatory effects and G_βγ‐mediated cell death