2016.10.21

By

Fluoxetine Ameliorates Atopic Dermatitis-Like Skin Lesions in BALB/c Mice through Reducing Psychological Stress and Inflammatory Response

Yanxi Li,1,2,3,† Long Chen,1,2,† Yehong Du,1,2,† Daochao Huang,1,2 Huili Han,1,2 and Zhifang Dong1,2,*
Author information ► Article notes ► Copyright and License information ►
Go to:

Abstract

Atopic dermatitis (AD) is a common chronic inflammatory skin disorder, and patients with AD suffer from severe psychological stress, which markedly increases the prevalence rate of depression and anxiety disorders in later life. Fluoxetine, a selective serotonin reuptake inhibitor, has recently been reported to exert anti-inflammatory and immunosuppressive effects. However, it is unclear whether fluoxetine is effective in the treatment of AD through reducing psychological stress and inflammatory reaction. Here, we reported that a BALB/c mouse model of AD was induced by application of 2,4-dinitrochlorobenzene (DNCB) onto hairless dorsal skin. Chronic fluoxetine treatment (10 mg/kg per day, i.p.) significantly attenuated AD-like symptoms, as reflected by a dramatic decrease in scratching bouts, as well as a decrease in anxiety- and depressive-like behaviors. Furthermore, these behavioral changes were accompanied by a significant decrease in epidermal thickness, the number of mast cells in skin tissue, mRNA levels of interleukin-4 (IL-4) and IL-13 in the spleen, as well as serum immunoglobulin E (IgE) in the DNCB-treated mice by treatment with fluoxetine. Taken together, these results indicate that fluoxetine may suppress psychological stress and inflammatory response during AD development, and subsequently ameliorate AD symptoms, suggesting that fluoxetine may be a potential therapeutic agent against AD in clinic.

Fluoxetin ameliorates Atopic Dermatitis like skin lesions in BALB.c mice through reducing psychological stress and Inflammatory response

Journal club 16.10.07

By

Ethanol Extract of Sanguisorbae Radix Inhibits Mast Cell Degranulation and Suppresses 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis-Like Skin Lesions.

Ju-Hye Yang, Jae-Myung Yoo, Won-Kyung Cho, and Jin YeulMa
  • 1Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, 70 Cheomdan-ro, Dong-gu, Daegu 41062, Republic of Korea.

Abstract

Sanguisorbae Radix (SR) is well known as herbal medicine named “Zi-Yu” in Korea, which is the dried roots of Sanguisorba officinalis L. (Rosacease). We investigated the underlying mechanism on the inhibition of atopic dermatitis (AD) of an ethanol extract of SR (ESR) using 2,4-dinitrochlorobenzene- (DNCB-) induced AD mice model. Oral administration of ESR significantly suppressed DNCB-induced AD-like symptoms such as scratching behavior, ear thickness, epidermal thickness, and IgE levels. To investigate the effects of ESR treatment on degranulation of IgE/Ag-activated mouse bone marrow-derived mast cells (BMMCs), we measured the release of β-hexosaminidase (β-HEX, degranulation marker). ESR decreased the infiltration of eosinophils and mast cells into the AD skin lesions. Furthermore, ESR significantly inhibited degranulation of IgE/Ag-activated BMMCs. We have demonstrated that ESR decreased AD symptoms in mice and inhibits degranulation of IgE/Ag-activated mast cells. Our study suggests that ESR may serve as a potential therapeutic candidate for the treatment of AD symptoms.

Ethanol Extract of Sanguisorbae Radix Inhibits Mast Cell Degranulation and Suppresses 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis-Like Skin Lesions.

2016.09.30

By

Involvement of TRPV1 and TDAG8 in pruriception associated with noxious acidosis.

Lin SH1, Steinhoff M2, Ikoma A3, Chang YC4, Cheng YR5, Chandra Kopparaju R6, Ishii S7, Sun WH4, Chen CC8.

involvement of trpv1 and tdag8 in pruriception associated with noxious acidosis

Itch and pain are closely related but distinct sensations. Intradermal injection of acid generates pain in both rodents and humans; however, few studies have addressed the intriguing question of whether proton can evoke itch like other algogens at the basis of spatial contrast activation of single nociceptors. Here, we report that (1) citric acid (0.2 M) pH-dependently induced a scratching response in mice when applied intradermally to nape or cheek skin; (2) acidified buffer elevated intracellular calcium levels in dorsal root ganglion (DRG) pruriceptors; (3) injection of intradermal citric acid (pH 3.0) into the nape induced a pruritogen-like but not algogen-like c-Fos immunoreactivity pattern in the cervical spinal cord. Using pharmacological and genetic approaches, we identified potential acid-sensing channels/receptors involved in acidic citrate-evoked itch. Results indicate that TRPV1 but neither ASIC3 nor TRPA1 are involved in the acidic citrate-induced scratching response. Furthermore, one of the proton-sensing G-protein-coupled receptors, TDAG8, was highly (∼71%) expressed in Nppb+ DRG pruriceptors. Acidic citrate but not α-methyl-5-HT, chloroquine, compound 48/80 or bile acid-induced itch was markedly decreased in TDAG8-/- mice. In a heterologous expression system, TDAG8 potentiated the acid-induced calcium response by regulating TRPV1. Thus, proton could evoke pruriception by acting on TDAG8 to regulate TRPV1 activation with its mechanism of future therapeutic relevance.

2016.09.09

By

Coagulation-driven platelet activation reduces cholestatic liver injury and fibrosis in mice.

Joshi N1, Kopec AK, O’Brien KM, Towery KL, Cline-Fedewa H, Williams KJ, Copple BL, Flick MJ, Luyendyk JP.

Author information

Abstract

BACKGROUND:

The coagulation cascade has been shown to participate in chronic liver injury and fibrosis, but the contribution of various thrombin targets, such as protease activated receptors (PARs) and fibrin(ogen), has not been fully described. Emerging evidence suggests that in some experimental settings of chronic liver injury, platelets can promote liver repair and inhibit liver fibrosis. However, the precise mechanisms linking coagulation and platelet function to hepatic tissue changes following injury remain poorly defined.

OBJECTIVES:

To determine the role of PAR-4, a key thrombin receptor on mouse platelets, and fibrin(ogen) engagement of the platelet αII b β3 integrin (αIIb β3 ) in a model of cholestatic liver injury and fibrosis.

METHODS:

Biliary and hepatic injury was characterized following 4 week administration of the bile duct toxicant α-naphthylisothiocyanate (ANIT) (0.025%) in PAR-4-deficient mice, mice expressing a mutant form of fibrin(ogen) incapable of binding integrin αII b β3 (Fibγ(Δ5) ), and wild-type mice.

RESULTS:

Elevated plasma thrombin-antithrombin and serotonin levels, hepatic fibrin deposition, and platelet accumulation in liver accompanied hepatocellular injury and fibrosis in ANIT-treated wild-type mice. PAR-4 deficiency reduced plasma serotonin levels, increased serum bile acid concentration, and exacerbated ANIT-induced hepatocellular injury and peribiliary fibrosis. Compared with PAR-4-deficient mice, ANIT-treated Fibγ(Δ5) mice displayed more widespread hepatocellular necrosis accompanied by marked inflammation, robust fibroblast activation, and extensive liver fibrosis.

CONCLUSIONS:

Collectively, the results indicate that PAR-4 and fibrin-αII b β3 integrin engagement, pathways coupling coagulation to platelet activation, each exert hepatoprotective effects during chronic cholestasis.

Coagulation-deiven platelet activation reduces cholestasic liver injury and fibrosis in mice supplementary datas

2016.08.26

By

Faciliation of TRPV4-TRPV1 itch Science Signaling 2016.full

Authors: Seungil Kim, Devin M. Barry, Xian-Yu Liu, Shijin Yi, Admire Munanairi, Qing-Tao Meng, Wei Cheng, Ping Mo, Li Wan, Shen-Bin Liu, Kasun Ratnayake, Zhong-Qiu Zhao, Narasimhan, GautamJie Zheng, W. K. Ajith Karunarathne, Zhou-Feng Chen

 

The transient receptor potential channels (TRPs) respond to chemical irritants and temperature. TRPV1 responds to the itch-inducing endogenous signal histamine, and TRPA1 responds to the itch-inducing chemical chloroquine. We showed that, in sensory neurons, TRPV4 is important for both chloroquine and histamine-induced itch and that TRPV1 has a role in chloroquine-induced itch. Chloroquine-induced scratching was reduced in mice in which TRPV1 was knocked down or pharmacologically inhibited. Both TRPV4 and TRPV1 were present in some sensory neurons. Pharmacological blockade of either TRPV4 or TRPV1 significantly attenuated the Ca2+ response of sensory neurons exposed to histamine or chloroquine.
Knockout of Trpv1 impaired Ca2+ responses and reduced scratching behavior evoked by a TRPV4 agonist, whereas knockout of Trpv4 did not alter TRPV1-mediated capsaicin responses. Electrophysiological analysis of human embryonic kidney (HEK) 293 cells coexpressing TRPV4 and TRPV1 revealed that the presence of both channels enhanced the activation kinetics of TRPV4 but not of TRPV1. Biochemical and biophysical studies suggested a close proximity between TRPV4 and TRPV1 in dorsal root ganglion neurons and in cultured cells. Thus, our studies identified TRPV4 as a channel that contributes to both histamine- and chloroquine-induced itch and indicated that the function of TRPV4 in itch signaling involves TRPV1-mediated facilitation. TRP facilitation through the formation of heteromeric complexes could be a prevalent mechanism by which the vast array of somatosensory information is encoded in sensory neurons.

2016.08.19

By

Title: Stimulation of the histamine 4 receptor upregulates thymic stromal lymphopoietin (TSLP) in human and murine keratinocytes
Author: Katrin Schaper Dr. Kristine Rossbach Brigitta K¨other Holger Stark Manfred Kietzmann Thomas Werfel Ralf Gutzmer

 

Abstract
The cytokine thymic stromal lymphopoietin (TSLP) is involved in the development and the
progression of allergic diseases. It is mainly released by epithelial cells at barriers such as skin
and gut in response to danger signals. Overexpression of TSLP in keratinocytes (KC) can
Keratinocyte can provoke the development of a type 2 inflammatory response. Additionally, TSLP directly acts on sensory neurons and thereby triggers itch. Since histamine is also increased in lesions of inflammatory skin diseases, the aim of this study was to investigate possible effects of histamine as well as different histamine receptor subtype agonists and antagonists on TSLP production in KC. We therefore stimulated human KC with histamine in the presence or absence of the known TSLP-inductor poly I:C and measured TSLP production at protein as well as mRNA level. Histamine alone did not induce TSLP production in human KC, but preincubation with histamine prior to challenge with poly I:C resulted in a significant increase of TSLP production compared to stimulation with poly I:C alone. Experiments with different histamine receptor agonists (H1R: 2-pyridylethylamine ; H2R: amthamine; H2R/H4R: 4-
methylhistamine (4MH)) revealed a dominant role for the H4R receptor, as 4-MH in
combination with poly I:C displayed a significant increase of TSLP secretion, while the other
agonists did not show any effect. The increase in TSLP production by 4MH was blocked with
the H4R antagonist JNJ7777120. This effect was reproducible also in the murine KC cell line
MSC.
Taken together, our study indicates a new role for the H4 receptor in the regulation of TSLP
in keratinocytes. Therefore, blocking of the H4R receptor in allergic diseases might be
promising to alleviate inflammation and pruritus via TSLP.
Keywords: TSLP, histamine, histamine 4 receptor, keratinocytes

 

Stimulation of the histamine 4 receptor upregulates thymic stromal lymphopoietin (TSLP) in human and murine keratinocytes

2016.08.05

By

Proteinase-activated receptor 1 contributed to up-regulation of enkephalin in keratinocytes of patients with obstructive jaundice.

Tao KM , Tao Y , Chen CY , Yang LQ , Lu ZJ , Sun YM , Huang SD , Yu WF

ABSTRACT
Background: Skin synthesis of endogenous opioids such as enkephalin is considered to be increased in cholestatic rodents, which may induce antinociception in cholestatic liver disease. No studies have reported yet the expression of skin enkephalin in patients with cholestasis.

 
Methods: Electrical pain threshold, postoperative morphine consumption, and skin enkephalin expression were measured in patients with jaundice (n = 18) and control patients (n = 16). Male Sprague–Dawley rats (n = 52) and human keratinocyte cell line HaCaT were used in vivo and in vitro studies, respectively. Nociceptive thresholds and plasma and skin levels of methionine-enkephalin were compared in protease-activated receptors-1–antagonized and control bile duct–ligated rats. In in vitro study, the effect on thrombin-induced enkephalin expression was examined and the role of extracellular regulated protein kinases 1/2 and p38 was investigated.

 
Results: The authors found that: (1) the electrical pain threshold (mean ± SD) was 1.1 ± 0.1 mA in control patients, whereas it was significantly increased in patients with jaundice (1.7 ± 0.3 mA); 48-h postoperative morphine consumption was approximately 50% higher in the control group than that in the group with jaundice; (2) Skin keratinocytes enkephalin expression
was increased in the patients with jaundice; (3) Protease-activated receptors-1 antagonist 1 μg·kg−1·day−1 treatment to the bile duct–ligated rats significantly reduced plasma levels of methionine-enkephalin, nociceptive thresholds, and keratinocytes enkephalin expression; and (4) protease-activated receptors-1 activation induced enkephalin expression through phosphorylation of extracellular regulated protein kinases 1/2 and p38 in keratinocytes.

 
Conclusion: Protease-activated receptors-1 activation in peripheral keratinocytes may play an important role in the local synthesis of enkephalin during cholestasis.

Proteinasse-acticated receptor 1 contributed to up-regulation of enkephalin in keratinocytes of patients with jaundice

2016.07.22

By

Dioscin protects against ANIT-induced cholestasis via regulating Oatps, Mrp2 and Bsep expression in rats.

Zhang A1, Jia Y2, Xu Q3, Wang C4, Liu Q5, Meng Q6, Peng J7, Sun H8, Sun P9, Huo X10, Liu K11.

Abstract

Alpha-naphthylisothiocyanate (ANIT) is a toxicant that is widely used in rodents to model human intrahepatic cholestasis. The aim of the study is to investigate whether effects of dioscin on ANIT-induced cholestasis are related to changes in expression of hepatic transporters in rats. Effects of dioscin on cholestasis were examined by histology and biochemical marker levels. The functional changes of hepatic transporters were determined by in vitro, in situ and in vivo. qRT-PCR and western blot were used to assess the expression of hepatic transporters in cholestatic rats. Dioscin administration could ameliorate cholestasis, as evidenced by reduced biochemical markers as well as improved liver pathology. The uptakes of organic anion transporting polypeptide (Oatp) substrates were altered in liver uptake index in vivo, perfused rat liver in situ and isolated rat hepatocytes in vitro in cholestasis rats. qRT-PCR and western blot analysis indicated co-treatment of ANIT with dioscin prevented the adaptive down-regulation of Oatp1a1, 1b2, and prompted the up-regulation of Oatp1a4, multidrug resistance-associated protein (Mrp) 2 and bile salt export pump (Bsep). In addition, concerted effects on Mrp2 and Bsep occurred through up-regulation of small heterodimer partner by activating farnesoid X receptor. Dioscin might prevent impairment of hepatic function by restoring hepatic transporter expression.

Dioscin protects against ANIT-induced cholestasis via regulating Oatps. Mrp2 and Bsep expression in rats

2016.07.15

By

Rhinovirus upregulates transient receptor potential channels in a human neuronal cell line: implications for respiratory virus-induced cough reflex sensitivity.

Abdullah H1, Heaney LG, Cosby SL, McGarvey LP.

Abstract

BACKGROUND:

The mechanism underlying respiratory virus-induced cough hypersensitivity is unknown. Upregulation of airway neuronal receptors responsible for sensing physical and chemical stimuli is one possibility, and the transient receptor potential (TRP) channel family are potential candidates. We have used an in vitro model of sensory neurons and human rhinovirus (HRV-16) to study the effect of virus infection on TRP expression.

METHODS:

IMR-32 neuroblastoma cells were differentiated in culture to express three TRP channels: TRPV1, TRPA1 and TRPM8. Flow cytometry and qRT-PCR were used to measure TRP channel protein and mRNA levels following inoculation with live virus, inactivated virus, virus-induced soluble factors or pelleted virus particles. Multiplex bioassay was used to determine nerve growth factor (NGF), interleukin (IL)-1β, IL-6 and IL-8 levels in response to infection.

RESULTS:

Early upregulation of TRPA1 and TRPV1 expression occurred 2-4 h post infection. This was independent of replicating virus as virus-induced soluble factors alone were sufficient to increase channel expression 50-fold and 15-fold, respectively. NGF, IL-6 and IL-8 levels, increased in infected cell supernatants, represent possible candidates. In contrast, TRPM8 expression was maximal at 48 h (9.6-fold) and required virus replication rather than soluble factors.

CONCLUSIONS:

We show for the first time that rhinovirus can infect neuronal cells. Furthermore, infection causes upregulation of TRP channels by channel-specific mechanisms. The increase in TRPA1 and TRPV1 levels can be mediated by soluble factors induced by infection whereas TRPM8 requires replicating virus. TRP channels may be novel therapeutic targets for controlling virus-induced cough.

Rhinovirus upregulates TRP

2016.07.01

By

Increased ZAP70 Is Involved in Dry Skin Pruritus in Aged Mice

Nan Zhao,1 Min Gu,2 Wenxiu Yang,1 Man Zhang,2 Qi Tian,2 Liyan Ru,1 Yang Lü,2 and Weihua Yu1

1Institute of Neuroscience, Department of Human Anatomy, Chongqing Medical University, Chongqing 400016, China
2Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China

 

Abstract

Dry skin pruritus is common in the elderly. Recent reports show that T-cell signal path is involved in dry skin pruritus. Zeta-chain-associated protein kinase 70 (ZAP70), as a T-cell receptor, may induce interleukin 2 (IL-2) secretion and promote nerve growth factor (NGF) secretion in skin. This study aimed to detect the alteration of ZAP70 in a mice model with dry skin pruritus. The C57BL mice with 5 months and 22 months were used as experimental animal. Following a 5-day period of treatment of back with a mixture of acetone-diethyl-ether-water (AEW), mice exhibited a significant increase in spontaneous scratching behavior directed to the treated back compared to control animals in which back was similarly treated with water only (W). After AEW process, spontaneous scratching in 22-month AEW mice was increased compared to 5-month AEW mice. Western blot and real-time quantitative PCR data analysis showed that ZAP70 expression was significantly increased in 22-month AEW mice compared with 5-month AEW mice. ELISA data showed that secretions of IL-2 and NGF in 22-month AEW mice were higher than 5-month AEW mice. Our results indicate that increased ZAP70 is involved in dry skin in elderly pruritus. Increased secretion of IL-2 and NGF may induce dry skin itch.

Increased ZAP70 Is Involved in Dry Skin Pruritus in Aged Mice.

Scroll to Top