Decreased cyclic AMP in the epidermis of lesions of psoriasis

Voorhees, John J.

doi:10.1001/archderm.105.5.695

Cited by 49 publications

(26 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Studies by Voorhees and colleagues and Flaxman and Harper over 30 years ago demonstrated the regulation of keratinocyte proliferation by intracellular levels of cAMP, and that elevation of intracellular cAMP by catecholamine stimulation resulted in a decrease in proliferation [8,9,[63][64][65]. Work by these laboratories also suggested that a decrease in the ability of psoriatic keratinocytes to respond to beta adrenergic agonists with an increase in cAMP could be, in part, responsible for the increase in cell proliferation characteristic of the disease [66][67][68][69]. These studies relied on keratome sections of psoriatic epidermis, but a later study by Iizuka and colleagues demonstrated similar findings in epidermis microdissected from involved psoriatic skin free of stratum corneum, dermis and appendages.…”

Section: Psoriasismentioning

confidence: 99%

Beta Adrenergic Receptors in Keratinocytes

Sivamani

Lam

Isseroff

2007

Dermatologic Clinics

View full text Add to dashboard Cite

SynopsisBeta2 adrenergic receptors were identified in keratinocytes more than 30 years ago, but their function in the epidermis continues to be elucidated. Abnormalities in their expression, signaling pathway, or in the generation of endogenous catecholamine agonists by keratinocytes have been implicated in the pathogenesis of cutaneous diseases such as atopic dermatitis, vitiligo and psoriasis. New studies also indicate that the beta2AR also modulates keratinocyte migration, and thus can function to regulate wound re-epithelialization. This review focuses on the function of these receptors in keratinocytes and their contribution to cutaneous physiology and disease.Keywords beta-adrenergic; keratinocyte; atopic dermatitis; psoriasis; vitiligo; wound Physiology of the beta2 adrenergic receptor in keratinocytesOf the several identified classes of adrenergic receptors (alpha and beta, and their subtypes), it is of particular interest to note that human keratinocytes, the cells the make up the majority of the epidermis, express only beta2 adrenergic receptors (beta2AR) [1][2][3][4]. The beta adrenergic receptor is a classic seven transmembrane G protein coupled receptor. These receptors serve as the endogenous receptor to the catecholamine hormones norepinephrine and epinephrine, and can be further subdivided into beta1, beta2, and beta3 subtypes, based on their differential pharmacological response to catecholamines and specific antagonists, as well as differences in their protein sequences [5][6][7].The first studies to suggest the presence of betaAR in the epidermis were functional ones that demonstrated an increase in levels of cAMP in keratinocytes after stimulation with non-specific betaAR agonists [8,9]. Subsequently, work using agonists and antagonists with specificity for the different adrenergic receptor subtypes demonstrated that the increase in keratinocyte

show abstract

Section: Psoriasismentioning

confidence: 99%

Beta Adrenergic Receptors in Keratinocytes

Sivamani

Lam

Isseroff

2007

Dermatologic Clinics

View full text Add to dashboard Cite

show abstract

“…Two lines of research grew simultaneously. The first was devoted to find out intrinsic keratinocyte abnormalities: extensive biochemical studies performed in the seventies demonstrated several defects of the psoriatic keratinocyte, most of them concerning the ‘cellular second messengers’, the role of which in cellular physiology had just been discovered [2, 3, 4]. At the same time, the second line of research was interested in immune disturbances associated with the disease: we and others demonstrated abnormal humoral and cellular immune responses [5, 6, 7, 8, 9]and strong association of psoriasis with histocompatibility antigens [10, 11].…”

Section: Introductionmentioning

confidence: 99%

Immunopathogenesis of Psoriasis: News in an Old Concept

Guilhou

1998

Dermatology

View full text Add to dashboard Cite

Twenty years ago, a concept of psoriasis pathogenesis was proposed in which epidermal proliferation of psoriatic lesions was the consequence of immunological abnormalities. This concept has subsequently been supported by the remarkable efficacy of immunosuppressive drugs. Moreover, recent experimental data indicate that activated psoriatic lymphocytes are capable of inducing keratinocyte proliferation. However, we have still to explain the mechanism by which lymphocytes act on keratinocytes and to find out what antigenic material could be responsible for their activation.

show abstract

“…However, the role of cAMP signaling in the pathogenesis of psoriasis remains controversial, largely due to conflicting literature surrounding how cAMP signaling influences psoriasis. Initial studies reported a significant decrease in cAMP in psoriatic epidermis when compared to uninvolved and control epidermis [52][53][54], and that pharmacologic elevation of intracellular cAMP could suppress epidermal proliferation [55][56][57]. Later investigations, however, were not consistent, with some finding no difference in cAMP levels in psoriatic epidermis compared to normal epidermis [58,59] and still others confirming prior studies that did find a difference.…”

Section: Camp Signaling In Psoriasismentioning

confidence: 95%

Cyclic Adenosine Monophosphate Signalling in Inflammatory Skin Disease

Levy¹,

Zhou²

2015

J Clin Exp Dermatol Res

View full text Add to dashboard Cite

The second messenger cyclic adenosine monophosphate (cAMP) regulates numerous key pathways that impact the immune system. Distinct cellular cAMP signaling pathways can lead to both pro-and anti-inflammatory effects depending upon the cell type. When dysregulated, these cAMP pathways can influence the pathogenesis of inflammatory cutaneous diseases, such as atopic dermatitis and psoriasis. In psoriasis and atopic dermatitis, cAMP and/or its effector proteins (e.g., protein kinase A) are downregulated suggesting that elevation of cAMP might be a therapeutic option. cAMP levels are the result of balance between synthesis by adenylyl cyclases and degradation by phosphodiesterases (PDEs). Pharmacologically inhibiting PDEs represents one effective mechanism to raise intracellular cAMP levels perhaps leading to targeted immune suppression. Several drugs have been developed to target PDEs and while some toxicities (e.g., nausea and emesis) exist these drugs are generally well tolerated. Perhaps the best characterized is Apremilast, a PDE4 specific inhibitor, which has been FDA approved for the treatment of psoriasis and shows great promise as a safe and novel immunosuppressive medication. Following on the heels of Apremilast are numerous oral and topical PDE inhibitors in various stages of clinical trials. In this review, we examine the role of cAMP signaling in inflammatory cutaneous diseases and the development of PDE inhibitors as therapeutics.

show abstract

Decreased cyclic AMP in the epidermis of lesions of psoriasis

Cited by 49 publications

References 0 publications

Beta Adrenergic Receptors in Keratinocytes

Beta Adrenergic Receptors in Keratinocytes

Immunopathogenesis of Psoriasis: News in an Old Concept

Cyclic Adenosine Monophosphate Signalling in Inflammatory Skin Disease

Contact Info

Product

Resources

About