Trends in Pharmacological Sciences
Mast cells as targets of corticotropin-releasing factor and related peptides
Section snippets
A skin ‘brain’ and mast cells
It has often humorously been argued that the brain is an appendix of the skin! Recent evidence shows that many genes known to be expressed in the CNS are also expressed in vast epidermal domains of a hemichordate organism, suggesting the presence of a ‘skin brain’ [17]. Extensive neuroendocrinological associations in the skin have also been described [18]. Indeed, there are anatomical and functional interactions between peripheral nerves and mast cells in the skin [19]; studies suggest that
CRF and mast cell-dependent actions in the skin
There are fundamental differences between CRF signaling systems in human and rodent skin. Thus, although human skin expresses both CRF and Ucn mRNA, mouse skin cells produce only Ucn peptides; the most prevalent cutaneous stressor, UV radiation, can also stimulate CRF protein production by human skin cells 32, 33, 34. The gene encoding CRF is not expressed in mouse skin but the peptide is delivered to the skin by nerve endings [35]. Furthermore, human epidermis expresses predominantly CRF1
Mast cells, keratinocytes and infections
Typically, chronic stress attenuates immune processes whereas acute stress appears to stimulate these processes. This latter effect appears to involve mast cell activation [29] and re-distribution of leukocytes from the blood to the skin, leading to enhanced delayed hypersensitivity reactions [1]. Recent findings indicate that mast cells might be crucial for defense against bacterial infections. For example, adherent Escherichia coli activates mouse mast cells in vitro, whereas W/Wv mast
Conclusions and future directions
Mast cells have emerged recently as versatile effector cells in the regulation of numerous processes, including the regulation of immunity [2], inflammation, the blood–brain barrier [1] and cancer growth [16] (Figure 1). Skin and hypothalamic mast cells appear to have important physiological functions as sensors of stressful events with bidirectional regulation of the HPA axis; a local increase of the levels of CRF or Ucn in extracranial tissues under stress could adversely affect different
Acknowledgements
Aspects of this work were supported in part by grant No. AR47652 from the US NIH, to T.C.T. Thanks to Jessica Christian for her word processing skills. The possible therapeutic use of CRF receptor antagonists alone, or in combination with mast cell secretion inhibitors, in stress-induced dermatoses is covered by US Patents No. 6,020 305 and 6,689 748 awarded to T.C.T.
References (60)
- et al.
Critical role of mast cells in inflammatory diseases and the effect of acute stress
J. Neuroimmunol.
(2004) Roles of mast cells and basophils in innate and acquired immunity
Curr. Opin. Immunol.
(2000)Differential release of mast cell interleukin-6 via c-kit
Blood
(1997)Activation of human mast cells by aggregated IgG through FcγRI: additive effects of C3a
Clin. Immunol.
(2004)Immune sensitization in the skin is enhanced by antigen-independent effects of IgE
Immunity
(2004)- et al.
Mast cells: the JEKYLL and HYDE of tumor growth
Trends Immunol.
(2004) - et al.
Plasma extravasation in the skin and pelvic organs evoked by antidromic stimulation of the lumbosacral dorsal roots of the rat
Neuroscience
(1995) Stress-induced dura vascular permeability does not develop in mast cell-deficient and neurokinin-1 receptor knockout mice
Brain Res.
(2003)Identification, localization and receptor characterization of novel mammalian substance P-like peptides
Gene
(2002)- et al.
Corticotropin releasing factor receptor type 1: molecular cloning and investigation of alternative splicing in the hamster skin
J. Invest. Dermatol
(2002)
Acute immobilization stress triggers skin mast cell degranulation via corticotropin releasing hormone, neurotensin and substance P: A link to neurogenic skin disorders
Brain Behav. Immun.
Corticotropin-releasing factor-like immunoreactivity in sensory ganglia and capsaicin sensitive neurons of the rat central nervous system: colocalization with other neuropeptides
Peptides
NF-kappaB participates in the corticotropin-releasing, hormone-induced regulation of the pituitary proopiomelanocortin gene
J. Biol. Chem.
Morphological and functional demonstration of rat dura mast cell-neuron interactions in vitro and in vivo
Brain Res.
Corticotropin-releasing factor receptors: from molecular biology to drug design
Trends Pharmacol. Sci.
Functional characteristics of CRH receptors and potential clinical applications of CRH-receptor antagonists
Trends Endocrinol. Metab.
Intramuscular injection of hrRANTES causes mast cell recruitment and increased transcription of histidine decarboxylase: lack of effects in genetically mast cell-deficient W/Wv mice
FASEB J.
Stem cell factor is localized in, released from, and cleaved by human mast cells
J. Immunol.
IgE receptor-mediated release of nerve growth factor by mast cells
Clin. Exp. Allergy
Differential release of serotonin and histamine from mast cells
Nature
IL-1 induces vesicular secretion of IL-6 without degranulation from human mast cells
J. Immunol.
Human skin mast cell rapidly release preformed and newly generated TNF-alpha and IL-8 following stimulation with anti-IgE and other secretagogues
Exp. Dermatol.
Comparative cytokine profile of human skin mast cells from two compartments – strong resemblance with monocytes at baseline but induction of IL-5 by IL-4 priming
J. Leukoc. Biol.
IL-4 and -5 prime human mast cells for different profiles of IgE-dependent cytokine production
Proc. Natl. Acad. Sci. U. S. A.
T cells and mast cells as a major source of interleukin-13 in atopic dermatitis
Dermatology
Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes
J. Immunol.
Early central nervous system evolution: An era of skin brains?
Nat. Rev. Neurosci.
Neuroendocrinology of the skin
Endocr. Rev.
The role of mast cells in inflammatory processes: evidence for nerve mast cell interactions
Int. Arch. Allergy Appl. Immunol.
Direct neurite-mast cell communication in vitro occurs via the neuropeptide substance P
J. Immunol.
Cited by (280)
The peripheral corticotropin releasing factor family's role in vasculitis
2024, Vascular PharmacologyMast cells in the autonomic nervous system and potential role in disorders with dysautonomia and neuroinflammation
2023, Annals of Allergy, Asthma and ImmunologyMast Cells in Autism Spectrum Disorder—The Enigma to Be Solved?
2024, International Journal of Molecular SciencesPathophysiology of Chronic Pelvic Pain
2023, Textbook of Female Urology and Urogynecology: Clinical Perspectives