Pituitary adenylate cyclase‐activating polypeptide inhibits cutaneous immune function

Kodali, Sreedevi; Friedman, Ilyse; Ding, Wanhong; Seiffert, Kristina; Wagner, John A.; Granstein, Richard D.

doi:10.1002/eji.200324085

Cited by 24 publications

(32 citation statements)

References 54 publications

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“…These findings were recently confirmed in a study in which PACAP inhibited the induction of contact hypersensitivity by reducing murine LC antigen-presenting cell (primary and XS106 cell line) properties (441). Additionally, PACAP inhibits the LPS/granulocyte-macrophage colony stimulating factor (GM-CSF)-induced stimulation of IL-1␤ and augments IL-10, presumably by modulation of cytokine production (442). VIP and PACAP both inhibit the LPS-stimulated production of TNF-␣ via VPAC1R and activation of the adenylate cyclase system in vitro and in vivo, suggesting a protective role for VIP and PACAP regulating the release of TNF-␣ during inflammation (194,200).…”

Section: Pacapmentioning

confidence: 67%

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

Roosterman¹,

Goerge

Schneider

et al. 2006

Physiological Reviews

531

509

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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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Section: Pacapmentioning

confidence: 67%

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

Roosterman¹,

Goerge

Schneider

et al. 2006

Physiological Reviews

531

509

View full text Add to dashboard Cite

show abstract

“…In the epidermis, ␤ 2 adrenoreceptors are expressed by both LC and keratinocytes (36), raising the possibility that activation of these receptors may represent one mechanism for the rapid mobilization of cutaneous IL-10. In contrast, neuropeptides, such as pituitary adenylate cyclase-activating polypeptide and calcitonin gene-related peptide, inhibit cutaneous immune responses and are associated with the ability to enhance IL-10 production (37,38). In addition, mediators such as PGE 2 , histamine, and increased cAMP all favor IL-10 production and Th2 responses (4,5,39).…”

Section: Discussionmentioning

confidence: 99%

Impact of Cutaneous IL-10 on Resident Epidermal Langerhans’ Cells and the Development of Polarized Immune Responses

Cumberbatch

Clelland

Dearman

et al. 2005

The Journal of Immunology

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Prolonged topical exposure of BALB/c mice to chemical contact and respiratory allergens stimulates, respectively, preferential Th1- and Th2-type responses with respect to serum Ab isotype and cytokine secretion phenotypes displayed by draining lymph node cells. We now report that differential cytokine secretion patterns are induced rapidly in the skin following first exposure to the contact allergen 2,4-dinitrochlorobenzene (DNCB) and the respiratory sensitizer trimellitic anhydride (TMA). TMA induced early expression of IL-10, a cytokine implicated in the negative regulation of Langerhans cell (LC) migration, whereas exposure to DNCB resulted in production of the proinflammatory cytokine IL-1β. Associated with this, TMA provoked LC migration with delayed kinetics compared with DNCB, and local neutralization of IL-10 caused enhanced LC mobilization in response to TMA with concomitant up-regulation of cutaneous IL-1β. We hypothesize that these differential epidermal cytokine profiles contribute to the polarization of immune responses to chemical allergens via effects on the phenotype of activated dendritic cells arriving in the draining lymph node. Thus, TMA-exposed dendritic cells that have been conditioned in vivo with IL-10 (a potent inhibitor of the type 1-polarizing cytokine IL-12) are effective APCs for the development of a Th2-type response.

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“…Furthermore, it has been demonstrated that these nerves are capable of releasing peptides that regulate LC function (1). Several neuropeptides, including calcitonin gene-related peptide, ␣-melanocyte-stimulating hormone, and pituitary adenylate cyclase-activating polypeptide (PACAP), have been shown to inhibit LC immune function (1)(2)(3)(4)(5)(6). In vivo, both calcitonin gene-related peptide and PACAP inhibited the induction of contact hypersensitivity and elicitation of delayedtype hypersensitivity (DTH) (1,3,6).…”

mentioning

confidence: 99%

“…Several neuropeptides, including calcitonin gene-related peptide, ␣-melanocyte-stimulating hormone, and pituitary adenylate cyclase-activating polypeptide (PACAP), have been shown to inhibit LC immune function (1)(2)(3)(4)(5)(6). In vivo, both calcitonin gene-related peptide and PACAP inhibited the induction of contact hypersensitivity and elicitation of delayedtype hypersensitivity (DTH) (1,3,6). In vitro, they inhibited LC Ag presentation function and modulated LC cytokine production (1,2,6).…”

mentioning

confidence: 99%

“…In vivo, both calcitonin gene-related peptide and PACAP inhibited the induction of contact hypersensitivity and elicitation of delayedtype hypersensitivity (DTH) (1,3,6). In vitro, they inhibited LC Ag presentation function and modulated LC cytokine production (1,2,6). ␣-Melanocyte-stimulating hormone inhibits the induction and elicitation of contact hypersensitivity and induces hapten-specific tolerance (5).…”

mentioning

confidence: 99%

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Vasoactive Intestinal Peptide Modulates Langerhans Cell Immune Function

Kodali¹,

Ding²,

Huang³

et al. 2004

The Journal of Immunology

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Epidermal nerves lie in close proximity to Langerhans cells (LC) and are capable of releasing peptides that modulate LC function, including calcitonin gene-related peptide and pituitary adenylate cyclase-activating polypeptide. The neuropeptide vasoactive intestinal peptide (VIP) has also been found in cutaneous nerves and mRNA, for the VIP receptor vasoactive intestinal peptide receptor type 1, and vasoactive intestinal peptide receptor type 2 have been found in murine LC and the LC-like cell line XS106. We examined the effects of VIP on LC function and cutaneous immunity. VIP inhibited elicitation of a delayed-type hypersensitivity response in previously immunized mice by epidermal cells enriched for LC content pulsed with Ag in vitro. VIP also inhibited the ability of unseparated epidermal cells to present Ag to a T cell clone and hybridoma and the ability of highly enriched LCs to present to the T cell clone. Inhibition of presentation to the hybridoma was observed with an antigenic peptide that does not require processing, suggesting that VIP is active at a step independent of Ag processing. To elucidate the mechanism(s) by which VIP may mediate these effects, we determined the effects of VIP on LC cytokine production using the XS106 cell line as a surrogate for LC. VIP augmented the production of the IL-10 in LPS-stimulated XS106 cells while down-regulating IL-12 and IL-1β production. Thus, VIP, like pituitary adenylate cyclase-activating polypeptide and calcitonin gene-related peptide, down-regulates LC function and the associated immune response.

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Pituitary adenylate cyclase‐activating polypeptide inhibits cutaneous immune function

Cited by 24 publications

References 54 publications

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

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

Impact of Cutaneous IL-10 on Resident Epidermal Langerhans’ Cells and the Development of Polarized Immune Responses

Vasoactive Intestinal Peptide Modulates Langerhans Cell Immune Function

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