Substance P Is Diminished and Vasoactive Intestinal Peptide Is Augmented in Psoriatic Lesions and These Peptides Exert Disparate Effects on the Proliferation of Cultured Human Keratinocytes

Pincelli, Carlo; Fantini, Fabrizio; Romualdi, Patrizia; Sevignani, Cinzia; Lesa, Giovanni; Benassi, Luisa; Giannetti, Alberto

doi:10.1111/1523-1747.ep12499846

Cited by 119 publications

(79 citation statements)

References 52 publications

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“…59 -61 Moreover, the growth-promoting effects of substance P on keratinocytes are concentration-dependent and may rely on the presence of additional growth modulators in the culture medium. 62,63 In an in situ context, ie, in a physiological epithelial-mesenchymal interaction milieu containing degranulating dermal mast cells, inhibition of keratinocyte proliferation has been shown before at concentrations used in our study. 42,55,64 Low levels of cortisol as observed under chronic stress or chronic inflammation may feed into SP skin signaling because it enhances SP production by keratinocytes.…”

Section: Discussionsupporting

confidence: 62%

Probing the Effects of Stress Mediators on the Human Hair Follicle

Peters

Liotiri

Bodó

et al. 2007

The American Journal of Pathology

169

150

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Stress alters murine hair growth, depending on substance P-mediated neurogenic inflammation and nerve growth factor (NGF), a key modulator of hair growth termination (catagen induction). Whether this is of any relevance in human hair follicles (HFs) is completely unclear. Therefore, we have investigated the effects of substance P, the central cutaneous prototypic stress-associated neuropeptide, on normal, growing human scalp HFs in organ culture. We show that these prominently expressed substance P receptor (NK1) at the gene and protein level. Organcultured HFs responded to substance P by premature catagen development, down-regulation of NK1, and up-regulation of neutral endopeptidase (degrades substance P). This was accompanied by mast cell degranulation in the HF connective tissue sheath , indicating neurogenic inflammation. Substance P down-regulated immunoreactivity for the growthpromoting NGF receptor (TrkA) , whereas it up-regulated NGF and its apoptosis-and catagen-promoting receptor (p75NTR). In addition , MHC class I and ␤2-microglobulin immunoreactivity were up-regulated and detected ectopically, indicating collapse of the HF immune privilege. In conclusion, we present a simplistic, but instructive, organ culture assay to demonstrate sensitivity of the human HF to key skin stress mediators. The data obtained therewith allow one to sketch the first evidence-based biological explanation for how stress may trigger or aggravate telogen effluvium and alopecia areata. (Am J Pathol

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Section: Discussionsupporting

confidence: 62%

Probing the Effects of Stress Mediators on the Human Hair Follicle

Peters

Liotiri

Bodó

et al. 2007

The American Journal of Pathology

169

150

View full text Add to dashboard Cite

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“…Investigators have also reported increased levels of neuropeptides and sensory nerves in psoriatic skin lesions, and capsaicin, a chemical that depletes neuropeptides from nerve endings, has been reported to have some therapeutic value in clearing lesions (59,244). Increased concentrations or immunoreactivity for several neuropeptides have been observed in lesional skin of patients with psoriasis (10,154,572,573,643,809). Interestingly, an increase of both VIP-and CGRP-immunoreactive fibers was observed in lesional skin of patients with atopic dermatitis of the "high-stress" group.…”

Section: B Psoriasismentioning

confidence: 99%

Neuronal Control of Skin Function: The Skin as a Neuroimmunoendocrine Organ

Roosterman¹,

Goerge

Schneider

et al. 2006

Physiological Reviews

531

508

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This review focuses on the role of the peripheral nervous system in cutaneous biology and disease. During the last few years, a modern concept of an interactive network between cutaneous nerves, the neuroendocrine axis, and the immune system has been established. We learned that neurocutaneous interactions influence a variety of physiological and pathophysiological functions, including cell growth, immunity, inflammation, pruritus, and wound healing. This interaction is mediated by primary afferent as well as autonomic nerves, which release neuromediators and activate specific receptors on many target cells in the skin. A dense network of sensory nerves releases neuropeptides, thereby modulating inflammation, cell growth, and the immune responses in the skin. Neurotrophic factors, in addition to regulating nerve growth, participate in many properties of skin function. The skin expresses a variety of neurohormone receptors coupled to heterotrimeric G proteins that are tightly involved in skin homeostasis and inflammation. This neurohormone-receptor interaction is modulated by endopeptidases, which are able to terminate neuropeptide-induced inflammatory or immune responses. Neuronal proteinase-activated receptors or transient receptor potential ion channels are recently described receptors that may have been important in regulating neurogenic inflammation, pain, and pruritus. Together, a close multidirectional interaction between neuromediators, high-affinity receptors, and regulatory proteases is critically involved to maintain tissue integrity and regulate inflammatory responses in the skin. A deeper understanding of cutaneous neuroimmunoendocrinology may help to develop new strategies for the treatment of several skin diseases.

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“…However, it appears that the amount of neuropeptides in normal skin is not suYcient for inducing marked mast cell activation, a conclusion based on the Wndings that capsaicin can induce only weak, if any, histamine release in skin ex vivo and in situ [71,184]. Nevertheless, the case is diVerent in chronic skin inXammation, since increased SP-positive nerve Wbers [128] and increased tissue levels of SP and VIP [36] have been measured in the psoriatic lesion, though there are reports showing only increased VIP levels in the lesional skin [5,149]. Accordingly, topical capsaicin cream has been reported to be eVective in the treatment of psoriatic plaques [9] and the mechanism for this beneWcial eVect may be that prolonged capsaicin treatment depletes neuropeptides from nerves [178].…”

Section: Interactions Between Mast Cells and Sensory Nerves In Psoriasismentioning

confidence: 99%

Is there a role for mast cells in psoriasis?

et al. 2008

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Mast cells have traditionally been considered as eVector cells in allergy but during the last decade it has been realized that mast cells are essentially involved in the mechanisms of innate and acquired immunity. Upon activation by anaphylactic, piecemeal degranulation or degranulation-independent mechanisms mast cells can secrete rapidly or slowly a number of soluble mediators, such as serine proteinases, histamine, lipid-derived mediators, cytokines, chemokines and growth factors. Mast cells can express cell surface co-stimulatory receptors and ligands, and they can express MHC class II molecules and thereby present antigens. These soluble factors and cell surface molecules can interact with other cells, such as endothelial cells, keratinocytes, sensory nerves, neutrophils, T cell subsets and antigen presenting cells which are essential eVectors in the development of skin inXammation. Besides promoting inXammation, mast cells may attempt in some circumstances to suppress the inXammation and epidermal growth but the regulation between suppressive and proinXammatory mechanisms is unclear. Psoriasis is characterized by epidermal hyperplasia and chronic inXammation where tryptase-and chymase-positive MC TC mast cells are activated early in the developing lesion and later the cells increase in number in the upper dermis with concomitant expression of cytokines and TNF superfamily ligands as well as increased contacts with neuropeptide-containing sensory nerves. Due to the intimate involvement of mast cells in immunity and chronic inXammation the role of mast cells in psoriasis is discussed in this review.

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Substance P Is Diminished and Vasoactive Intestinal Peptide Is Augmented in Psoriatic Lesions and These Peptides Exert Disparate Effects on the Proliferation of Cultured Human Keratinocytes

Cited by 119 publications

References 52 publications

Probing the Effects of Stress Mediators on the Human Hair Follicle

Probing the Effects of Stress Mediators on the Human Hair Follicle

Neuronal Control of Skin Function: The Skin as a Neuroimmunoendocrine Organ

Is there a role for mast cells in psoriasis?

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