الفهرس 
Neuropeptides
• Factors affecting acne vulgarisOnly 14 pages are availabe for public view
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Abstract
Neuropeptides are defined as heterogeneous group of several hundred biologically active peptides that are present in neurons of both the central and peripheral nervous systems and that are involved in the transmission of signals, not only between nerve cells, but also in the immune system where they appear to be critical mediators of different processes.
Neuropeptides act as neuromodulators, neurotransmitters, hormones and neurohormones, and can manifest immunomodulatory activity. They contribute to the cross talk between the nervous and immune systems in the skin.
Various neuropeptides can be released from some somatic nerve fibers that innervate the skin (both: fine unmyelinated C-type and myelinated A-delta fibers) Upon stimulation whether physiological stimulations, such as physical stimuli (heat, cold, mechanical distension and UV radiation), or mechanical stimulations of low intensity these fibers are capable of releasing various neuroptides.
The major neuronal peptides of human skin include substance P (SP), substance K (SK), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), peptide histidine methionin (PHM), neuropeptide Y (NPY), somatostatin (SOM), neurotensin (NT), pituitary adenylate cyclase activating polypeptide (PACAP), proopiomelanocortin (POMC)-derived peptides and neurokinin A.
Substance P/ CGRP fibers are most abundant in fingers and toes. VIP fibers and NPY fibers are localized in the deeper parts of the dermis around blood vessels and acini of sweat glands. Fibers contaning these neuropeptides are also most common in fingertips and toes. VIP occurs in relatively high amounts in skin from the axilla, whereas NPY in this region was found to be below detection limit. Somatostatin-immunoreactive fibers were found in low concentrations in tissue extracts. Neuropeptides were found to play a role in the pathogenesis of certain skin diseases such as psoriasis, atopic dermatitis, prurigo nodularis, rosacea, vitiligo, eczema and acne vulgaris.
Acne Vulgaris is an extremely common chronic pilosebaceous disorder affecting almost 85% of adolescent and young adults aged 12–25. It results in both inflammatory and non-inflammatory clinical lesions and appear mainly on the face, chest, shoulders and back areas where the pilosebaceous unit has the greatest distribution.
Although not life-threatening and not a major player in clinical and laboratory research, acne markedly influences quality of life and constitutes a socio-economic problem as more than 15–30% of acne patients require medical treatment due to the severity of their clinical conditions. Being the most common disease affecting all ages and ethnic groups, acne is chosen to be the leading dermatologic diagnosis with 10.2 million diagnoses.
The pathogenesis of acne vulgaris is a multifactorial. The major contributing factors are: Abnormal follicular differentiation, increased cornification, enhanced sebaceous gland activity, bacterial hypercolonization, inflammation, androgens, skin lipids, regulatory neuro-peptides and immunological host reaction. Also, there is increasing evidence that hereditary factors play an important but an indirect role. On the other hand, ongoing researches are modifying the classical view of acne pathogenesis through identification of up-stream mechanisms leading to the phenotypic and laboratory findings.
There are 3 types of acne: comedonal, papulopustular, and nodular, all of which result from a multifactorial pathophysiologic process in the pilosebaceous unit: (1) sebum production, (2) follicular hyperkeratinization, (3) proliferation and colonization by Propionibacterium acnes and (4) the release of inflammatory mediators. Many factors affect pathogenesis of acne including genetic, foods, smoking, propionibacterium acnes, androgens and regulatory neuropeptides.
Inflammation occurs by activation of sensory nerves leading to secrete neuropeptides in various tissues, including the skin. Neuropeptides secreted in the skin are not only neurotransmitters of the pain and pruritus, but also play the role of the immune and inflammatory mediators. Several studies have demonstrated that MCs are often found in close contact with nerves and that there may be functional interactions between MCs and the nervous system.
The cytokines expressed by mast cells are primarily pro-inflammatory and are necessary for innate immunity [e.g. IL-1, IL-6, IL-8 and TNF-α]. Both the expression and the synthesis of these cytokines depend on: the state of maturation of the mast cells, the location of mast cells and the type of cytokines present during mast cell activation. SP contained within dermal nerve fibers may represent a crucial initial mediator of a cascade of cellular events involving MC degranulation and the release of proinflammatory cytokines such as TNF-α, with subsequent induction of adhesion molecules such as E-selectin on the adjacent venular endothelium. So, MC-derived SP may affect the morphologic and immunologic alterations associated with sebaceous glands and may contribute to the development inflammatory events in acne.
Substance P promotes both the proliferation and the differentiation of sebaceous glands. It also induces the expression of neutral endopeptidase, a potent neuropeptide-degrading enzyme, in sebaceous germinative cells with subsequent induction of adhesion molecules such as: E-selectin on perisebaceous venules. Facial skin of acne patients is rich in innervation compared with normal skin with increased numbers of SP-containing nerves, mast cells and by a strong expression of neutral endopeptidase in sebaceous glands also, with E-selectin in venules around sebaceous glands. Mast cell-derived IL-6 and TNF-α, followed by SP-stimulated degranulation, have the potential to induce nerve growth factor expression by sebaceous cells which results in the promotion of innervation and in the expression of E-selectin, respectively. SP enhances mast cell proliferation through up-regulation of stem cell factor expression in fibroblasts. These findings suggest the involvement of neurogenic factors, such as neuropeptides, in the disease process of acne and explain the possible mechanism of the exacerbation of acne from substance P.
Finally, many alterations in the distribution and levels of NPs have been demonstrated in various skin disorders as psoriasis, atopic dermatitis, vitiligo, nodular prurigo, urticaria, contact dermatitis and various inflammatory skin disorders. Substance P is an important neurotransmitter in peripheral sensory neurons, where it becomes in close opposition to the sebaceous glands promoting their proliferation and differentiation. Numerous lipid DROPlets were disintegrated by Substance P to form an acellular sebum secretion that stimulates sebaceous gland cells, even in the peripheral area of the glands. These observations indicate that SP can accelerate lipid synthesis and increase the number of sebum vacuoles in each differentiated sebaceous cell. Also, Substance P actively increases the release of sebaceous gland secretions which play a role in the pathogenesis of acne.