The prostaglandin D2 receptor CRTH2 is important for allergic skin inflammation after epicutaneous antigen challenge

He, Rui; Oyoshi, Michiko K.; Wang, Yen Tun; Hodge, Martin R.; Jin, Haoli; Geha, Raif S.

doi:10.1016/j.jaci.2010.07.006

Cited by 49 publications

(36 citation statements)

References 42 publications

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“…Additionally, CRTH2 has been implicated in the development of cutaneous inflammation as CRTH2 + CD4 + T cells and CRTH2 + eosinophils are increased in the blood of atopic dermatitis patients [13]. In mice, CRTH2 antagonists has been shown to effectively attenuate skin inflammation in various contact sensitivity models [14][15][16] including the oxazolone induced contact dermatitis model described in this report.…”

Section: Introductionmentioning

confidence: 72%

CRTH2 is Critical to the Development of Colitis Induced by Dextran Sodium Sulfate (DSS)

Ma¹

2012

J Clin Cell Immunol

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Chemoattractant Receptor-homologous molecule expressed on Th2 cells [CRTH2] is expressed on granulocytes (eosinophils, basophils and neutrophils), Th2 cells and monocytes. CRTH2 has been implicated in the development of cutaneous inflammation as CRTH2 + CD4 + T cells and CRTH2 + eosinophils are increased in the blood of atopic dermatitis patients. CRTH2 is also up-regulated in circulating neutrophils of psoriatic patients. Interestingly, CRTH2 is detected in the mucosa of patients with Inflammatory Bowel Disease (IBD) ulcerative colitis, where the CRTH2 positive cells localize within and adjacent to regions of inflamed mucosa suggesting that CRTH2 may play a role in IBD. However, the exact downstream inflammatory pathways resulting from CRTH2 activation in colitis are not well characterized. To gain a better understanding of the effects of CRTH2 activation in the pathogenesis of colitis, we have generated a small molecule inhibitor against CRTH2 and its potency was first validated in an oxazolone induced contact dermatitis model. We investigated the consequences of inhibiting CRTH2 in the development of IBD using a Dextran Sodium Sulfate (DSS)-induced colitis mouse model. Compared to the vehicle control group, mice treated with a selective CRTH2 antagonist had reduced disease severity as measured by weight loss, as well as serum acute phase protein, haptoglobin. Furthermore, pro-inflammatory cytokine gene expression for TNFα, IL-1β, IL-6, IL-17A, and IFNγ were reduced in colons of mice that had been treated with the CRTH2 antagonist compared with DSS treated controls that received vehicle. Taken together, our data identify a previously unrecognized role for CRTH2 in the initiation/amplification and/or stabilization of colon inflammation.

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Section: Introductionmentioning

confidence: 72%

CRTH2 is Critical to the Development of Colitis Induced by Dextran Sodium Sulfate (DSS)

Ma¹

2012

J Clin Cell Immunol

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“…In human skin, eicosanoids are generated and exert proinflammatory and immunoregulatory actions through their effects on blood vessels and inflammatory cells; eicosanoids are also involved in the regulation of growth and differentiation of the epidermis [22,23]. Therefore, eicosanoids have been suspected to contribute to the pathogenesis of a number of skin diseases such as atopic dermatitis [8,9,12,13], urticaria [10], psoriasis [7,11] and ultraviolet dermatitis [24]. The present data demonstrates a beneficial effect of a cPLA 2 inhibitor in DNFB-induced dermatitis, which further supports the linkage of cPLA 2 in the pathogenesis of skin inflammatory diseases.…”

Section: Discussionmentioning

confidence: 99%

Glutamine suppresses dinitrophenol fluorobenzene-induced allergic contact dermatitis and itching: Inhibition of contact dermatitis by glutamine

Jin

Kim

Lee

et al. 2012

Journal of Dermatological Science

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“…It is detected in the skin of AD patients 9, 10, 15, 16 as well as in the OVA-induced AD model 17 . PGD 2 production in skin can also be stimulated by scratching, however 18 .…”

Section: Prostanoids In Immunology Of Admentioning

confidence: 96%

Prostanoids in allergy

Honda

Kabashima

2015

Allergology International

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Prostanoids, which include prostaglandin and thromboxane, are metabolites of arachidonic acid released in various pathophysiological conditions. They induce a range of actions mediated through their respective receptors expressed on target cells. It has been demonstrated that each prostanoid receptor has multiple functions and that the effect of receptor stimulation can vary depending on context; this sometimes results in opposing effects, such as simultaneous excitatory and inhibitory outcomes. The balance between the production of each prostanoid and the expression of its receptors has been shown to be important for maintaining homeostasis but also involved in the development of various pathological conditions such as allergy. Here, we review the recent findings on the roles of prostanoids in allergy, especially focusing on atopic dermatitis and asthma.

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The prostaglandin D2 receptor CRTH2 is important for allergic skin inflammation after epicutaneous antigen challenge

Abstract: Background-Cutaneous PGD2 levels increase following scratching. CRTH2 mediates chemotaxis to PGD2 and is expressed on Th2 cells and eosinophils, which infiltrate skin lesions in atopic atopic dermatitis (AD).

Cited by 49 publications

References 42 publications

CRTH2 is Critical to the Development of Colitis Induced by Dextran Sodium Sulfate (DSS)

CRTH2 is Critical to the Development of Colitis Induced by Dextran Sodium Sulfate (DSS)

Glutamine suppresses dinitrophenol fluorobenzene-induced allergic contact dermatitis and itching: Inhibition of contact dermatitis by glutamine

Prostanoids in allergy

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