Transient receptor potential vanilloid 1 activation induces inflammatory cytokine release in corneal epithelium through MAPK signaling

Zhang, Fan; Yang, Hua; Wang, Zheng; Mergler, Stefan; Liu, Hongshan; Kawakita, Tetsuya; Tachado, Souvenir D.; Pan, Zhongdang; Capó-Aponte, José E.; Pleyer, Uwe; Koziel, Henry; Kao, Winston W.‐Y.; Reinach, Peter S.

doi:10.1002/jcp.21141

Cited by 124 publications

(114 citation statements)

References 42 publications

Supporting

Mentioning

105

Contrasting

Unclassified

Order By: Relevance

“…2d). Nevertheless, no difference in the expression of transient receptor potential vanilloid type 1 (Trpv1), which can also be activated by the endocannabinoid anandamide and can regulate lipogenesis [28], was revealed in adipose tissue of Cb2 −/− mice at 6 months of age (ESM Fig. 2e).…”

Section: Cb2mentioning

confidence: 99%

Deficiency of CB2 cannabinoid receptor in mice improves insulin sensitivity but increases food intake and obesity with age

et al. 2010

View full text Add to dashboard Cite

Aims/hypothesis The endocannabinoid system has a key role in energy storage and metabolic disorders. The endocannabinoid receptor 2 (CB2R), which was first detected in immune cells, is present in the main peripheral organs responsible for metabolic control. During obesity, CB2R is involved in the development of adipose tissue inflammation and fatty liver. We examined the long-term effects of CB2R deficiency in glucose metabolism. Methods Mice deficient in CB2R (Cb2 −/− [also known as Cnr2]) were studied at different ages (2-12 months). Twomonth-old Cb2 −/− and wild-type mice were treated with a selective CB2R antagonist or fed a high-fat diet.Results The lack of CB2R in Cb2 −/− mice led to greater increases in food intake and body weight with age than in Cb2 +/+ mice. However, 12-month-old obese Cb2 −/− mice did not develop insulin resistance and showed enhanced insulin-stimulated glucose uptake in skeletal muscle. In agreement, adipose tissue hypertrophy was not associated with inflammation. Similarly, treatment of wild-type mice with CB2R antagonist resulted in improved insulin sensitivity. Moreover, when 2-month-old Cb2 −/− mice were fed a high-fat diet, reduced body weight gain and normal insulin sensitivity were observed. Conclusions/interpretation These results indicate that the lack of CB2R-mediated responses protected mice from both age-related and diet-induced insulin resistance, suggesting that these receptors may be a potential therapeutic target in obesity and insulin resistance.

show abstract

Section: Cb2mentioning

confidence: 99%

Deficiency of CB2 cannabinoid receptor in mice improves insulin sensitivity but increases food intake and obesity with age

et al. 2010

View full text Add to dashboard Cite

show abstract

“…The TRPV1-4 members are moderately Ca 2+ selective (P Ca / P Na = 5-10) whereas the TRPV5-6 members are highly Ca 2+ selective (P Ca /P Na > 100) [30]. In HCEC, TRPC4 and TRPV1 functional expression was identified [31]. EGF-induced HCEC proliferation is dependent on activation of store operated channels containing TRPC4 whereas TRPV1 stimulation mediates inflammatory cytokine release via MAPK pathways [31,32].…”

Section: Introductionmentioning

confidence: 99%

“…In HCEC, TRPC4 and TRPV1 functional expression was identified [31]. EGF-induced HCEC proliferation is dependent on activation of store operated channels containing TRPC4 whereas TRPV1 stimulation mediates inflammatory cytokine release via MAPK pathways [31,32].…”

Section: Introductionmentioning

confidence: 99%

Dependence of regulatory volume decrease on transient receptor potential vanilloid 4 (TRPV4) expression in human corneal epithelial cells

et al. 2008

Self Cite

View full text Add to dashboard Cite

TRPV4 is a non-selective cation channel with moderate calcium permeability, which is activated by exposure to hypotonicity. Such a stress induces regulatory volume decrease (RVD) behavior in human corneal epithelial cells (HCEC). We hypothesize that TRPV4 channel mediates RVD in HCEC. Immunohistochemistry revealed centrally and superficially concentrated TRPV4 localization in the corneal tissue.Immunocytochemical and Fluorescence Activated Cell Sorter (FACS) analyses identified TRPV4 membrane surface and cytosolic expression. RT-PCR and Western blot analyses identified TRPV4 gene and protein expression in HCEC, respectively. In addition, 4α-PDD or a 50% hypotonic medium induced up to three-fold transient intracellular Ca 2+ ([Ca 2+ ] i ) increases. Following TRPV4 siRNA HCEC transfection, its protein expression level declined by 64%, which abrogated these [Ca 2+ ] i transients. Similarly, exposure to either ruthenium red or Ca 2+ -free Ringer's solution also eliminated this response. In these transfected cells, RVD declined by 51% whereas in the non-transfected counterpart, ruthenium red and Ca 2+ -free solution inhibited RVD by 54% and 64%, respectively. In contrast, capsazepine, a TRPV1 antagonist, failed to suppress [Ca 2+ ] i transients and RVD. TRPV4 activation contributes to RVD since declines in TRPV4 expression and activity are associated with suppression of this response. In conclusion, there is TRPV4 functional expression in HCEC.

show abstract

“…Such responses vary depending on the nature and intensity of the stimulus and some mediators have been pointed as major contributors in the process of ocular surface damage related to environmental factors. Members of the transient receptor potential (TRP) channel superfamily, which include subfamilies in corneal epithelial and keratocytes, respond to environmental irritants inducing afferent impulses to the central nervous system (79) . Chemical burns in mice induce a specific TRP vanilloid type 1 (TRPV1) channel deregulated inflammatory responses leading to corneal melt and opacification (80) .…”

mentioning

confidence: 99%

“…The injury-induced inflammatory and opacification responses resulting from TRPV1 activation were attributed to the up regulation of pro inflammatory and chemo attractive cytokines. TRPV1-induces downstream events by eliciting time dependent stimulation of the mitogen activated protein kinase (MAPK) cascade in epithelial cells and stromal fibroblasts (79,81) . Corneal epithelial wound is also accompanied by increased release of mitogens such as, epidermal growth factor (EGF), which induces cell proliferation and migration through activation of a TRP channel in the canonical subfamily identified as TRPC4 and MAPK signaling pathway (82)(83)(84)(85) .…”

mentioning

confidence: 99%

Is dry eye an environmental disease?

Alves¹,

Novaes²,

Morraye³

et al. 2014

Arquivos Brasileiros De Oftalmologia

View full text Add to dashboard Cite

Previous studies have revealed that eye contact with either air pollutants or adverse indoor and/or outdoor environmental conditions can affect tear film composition and ocular surface components. These effects are mediated by selective binding of the environmental agents to ocular surface membrane receptors, leading to activation of pro inflammatory signaling pathways. The aim of the current review was to examine the published evidence associated with environmental factors and ocular surface disease and dry eye. Specifically, the reader will appreciate why it is possible to refer to them as mediators of Environmental Dry Eye Disease (EDED), a singular clinical entity inside DED context, directly caused by pollutants and/ or adverse climatic conditions. The indicators and clinical findings are described along with EDE differential diagnosis in its acute and the chronic phases. Based on strong existing evidence of clinical reports and epidemiological observations regarding DED and environmental factors we conclude that there is a straight cause-and-effect relationship between ambient stresses and DED. International standards and web-based tools are described for monitoring worldwide environmental conditions referring localities and populations susceptible to EDED. This information is beneficial to health providers to pinpoint the individuals and predisposed groups afflicted with DED. Such insights may not only improve the understanding and treatment of DED but also help to identify the contributing factors and lower the frequency and progression of EDED. of DED has been studied and confirmed in animal models of human DED (13)(14)(15) . KeywordsAs indicated, a healthy and pain-free ocular surface depends on identifying and eliminating factors that cause ambient humidity, airflow and purity, and temperature to intolerable levels. Such an undertaking is needed to preserve tear film qualities commensurate with ocular surface health. This is essential to sustain sufficient corneal refractive power, visual acuity, and ocular comfort (5,16,17) . A desiccating environment can lead to increase in tear film evaporation and/or decline in its turn over and clearance. These initial events lead to exposure of the ocular surface to hazardous environmental elements that trigger or exacerbate EDED symptoms. Clinical findings have shown that increased numbers of people are affected by EDED because of exposure to environmental factors ( Figure 2).Our purpose herein is to provide a critical appraisal of the clinical and epidemiological evidence indicating that DED is influenced by environmental factors. Secondly, we delineate EDED as a single clinical entity with a unique set of symptoms and clinical findings different from that of either DED or other diseases, such as Sjögren's syndrome, diabetes mellitus or drug induced, allergic conjunctivitis, toxic or irritative conjunctivitis, and actinic keratitis. Moreover, we will describe standard tools used to monitor environmental conditions and discuss their relevance in EDED ep...

show abstract

Transient receptor potential vanilloid 1 activation induces inflammatory cytokine release in corneal epithelium through MAPK signaling

Cited by 124 publications

References 42 publications

Deficiency of CB2 cannabinoid receptor in mice improves insulin sensitivity but increases food intake and obesity with age

Deficiency of CB2 cannabinoid receptor in mice improves insulin sensitivity but increases food intake and obesity with age

Dependence of regulatory volume decrease on transient receptor potential vanilloid 4 (TRPV4) expression in human corneal epithelial cells

Is dry eye an environmental disease?

Contact Info

Product

Resources

About