title: Endocrinology of the skin: intradermal neuroimmune network, a new frontier.
abstract: Endocrinology systems exert an important effect on vascular function and have direct actions on blood vessels. Estrogens provoke an increase in skin elasticity, epidermal hydration, skin thickness, reduce skin wrinkles and augment the content of collagen and the level of vascularisation. Therefore, there is an intricate cross-talk between skin conditions and stress. In stress, β2--adrenoreceptor (β2AR) pathway, cortisol, epinephrine and norepinephrine increase DNA damage and interfere with the regulation of the cell cycle, contributing to aging and skin diseases. Substance P is a neuropeptide released in the skin from the peripheral nerve and is related to stress and inflammation. SP provokes infiltration of inflammatory cells in the skin and induces a variety of cytokines/chemokines. Corticotropin-releasing hormone (CRH), produced by mast cells, is a neuropeptide also expressed in skin and responds to stress. CRH initiates diverse intracellular signaling pathways, including cAMP, protein kinase C, and mitogen-activated protein kinases (MAPK). Under stress, CRH, glucocorticoids, epinephrine and cytokines are generated. Moreover, the release of ACTH binds the receptor MC2-R and stimulates the generation of glucocorticoids such as corticosterone and cortisol, which interact with the transcription factors AP-1 and NF-kB. In skin keratinocytes, ACTH promotes the generation of pro-inflammatory cytokines, which enhances T-cell activity. Cortisol is immunosuppressive by inhibiting Th1 and Th2 cell response, antigen presentation, antibody and cytokine/chemokine production. However, glucocorticoids are certainly helpful in Th1-mediated autoimmune disorders. On the other hand, cytokines, such as TNF, IL-1 and IL-6, stimulate the generation of CRH and activate HPA axis in inflammatory states. Here, we describe for the first time a cross-talk between endocrinology and skin, including pro-inflammatory cytokines and neurogenic inflammatory pathways.
authors.affiliation: University of Perugia, Perugia, Italy.
authors.forename: Al
authors.initials: Al
authors.lastname: Caraffa
authors.affiliation: Department of Surgery and Odontostomatological Sciences, University of Cagliari, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Spinas
authors.affiliation: Department of Microbiology and Infectious Diseases, School of Veterinary Medicine, Aristotle University of Thessaloniki, Macedonia, Greece.
authors.forename: S K
authors.initials: SK
authors.lastname: Kritas
authors.affiliation: Vascular Medicine Unit, Villa Serena Hospital, Citta' SantAngelo, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Lessiani
authors.affiliation: Clinica dei Pazienti del Territorio, Policlinico Gemelli, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Ronconi
authors.affiliation: Department of Dermatology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Saggini
authors.affiliation: Department of Orthopedics, Hospital, Perugia, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Antinolfi
authors.affiliation: University of Chieti, Chieti, Italy.
authors.forename: J
authors.initials: J
authors.lastname: Pizzicannella
authors.affiliation: Department of Medical, Oral and Biological Sciences, University of Chieti, Chieti, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Toniato
authors.affiliation: Molecular Immunopharmacology and Drug Discovery Laboratory, Tufts University, Boston, MA USA.
authors.forename: T C
authors.initials: TC
authors.lastname: Theoharides
authors.affiliation: Immunology Division, Medical School, University of Chieti-Pescara, Chieti, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Conti
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000502:physiology; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D004703:Endocrine System / Q000502:physiology*; D006801:Humans; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000276:immunology*; D013315:Stress, Psychological / Q000503:physiopathology; D013373:Substance P / Q000502:physiology
chemical_list: D016207:Cytokines; D013373:Substance P; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone