S179D prolactin diminishes the effects of UV light on epidermal gamma delta T cells (original) (raw)

2008, Molecular and Cellular Endocrinology

Langerhans cells (LC) are immune cells altered by exposure to ultraviolet radiation (UVB), a powerful stressor resulting in immune suppression. Prolactin (PRL) has been characterized as an immunomodulator, particularly during stress. In this study, we have asked whether separate administration of the two major forms of prolactin, unmodified and phosphorylated, to groups of 15 mice (3 experiments, each with 5 mice per treatment group) affected the number and morphology of these epidermal immune cells under control conditions, and following UV irradiation. Under control conditions, both PRLs reduced the number of γδ T, but a molecular mimic of phosphorylated PRL (S179D PRL) was more effective, resulting in a 30% reduction. In the irradiated group, however, S179D PRL was protective against a UV-induced reduction in γδ T number and change in morphology (halved the reduction and normalized the morphology). In addition, S179D PRL, but not unmodified (U-PRL), maintained a normal LC: γδ T ratio and sustained the dendritic morphology of LC after UV exposure. These findings suggest that S179D PRL may have an overall protective effect, countering UV-induced cellular alterations in the epidermis.

UVB irradiation modulates systemic immune responses by affecting cytokine production of antigen-presenting cells

International Immunology, 2000

The immunosuppressive effects of UVB irradiation have been well documented. The production of cytokines by keratinocytes is considered to play a major role in the induction of local as well as systemic immunosuppression. It is thought that partly due to the interaction of locally produced cytokines with antigen-presenting cells (APC) systemic effects, like antigen-specific tolerance, can be induced. In this study we examined the effect of UVB irradiation on cytokine profiles of peripheral APC as well as the functional consequences. Our results indicate that UVB irradiation impairs T h 1-mediated immune responses in vivo by suppression of the systemic IL-12p70 production. Splenic APC from UVB-exposed mice showed an enhanced production of prostaglandin E 2 , IL-1, IL-6 and tumor necrosis factor-α after in vitro stimulation. Also, spleen cells from UVB irradiated IL-4-/mice showed increased IL-6 levels. These APC were less efficient in inducing IFN-γ production by CD4 ⍣ T cells and suppressed IgM production by B cells. We conclude that the altered cytokine profile of peripheral APC can be responsible for the systemic effects of UVB irradiation on the T h 1/T h 2 balance as well as on B cell responses.

Immediate decrease in antigen-presenting function and delayed enhancement of interleukin-I production in human epidermal cells after in vivo UVB irradiation

British Journal of Dermatology, 1989

Human skin was irradiated in vivo with a single UVB dose (100 mj/cm^ or 200 mj/cm^) to examine simultaneously the antigen-presenting function and interleukin-1 (IL-i) production capacity of irradiated epidermal cells (EC). Suction blisters were produced on irradiated areas on days o, 3 and 7 after UVB. Irradiated EC were harvested and co-cultured with autologous T lymphocytes in the presence of antigens (PPD, HSV) or mitogen (ConA). Culture supernatants were tested for IL-i activity using the thymocyte comitogenity assay. We found that a single 200 mj/cm^ dose of UVB caused an immediate suppression of the antigenpresenting function of EC, but no alteration in their IL-i production capacity or surface marker expression (ATPase, CDi). PPD-and HSV-induced lymphocyte proliferation was decreased 70-80% and ConA-driven proliferation 30% when compared to non-irradiated EC. However, this suppression was restored on days 3 and 7 after UVB irradiation, this being coexistent with an increased capacity of EC to produce IL-i. It remains to be elucidated whether the immediate UVB-induced photoimmunosuppression observed in the present study is due to inhibitory mediators or impaired membrane function of EC or both.

Enhanced prostaglandin synthesis after ultraviolet injury is mediated by endogenous histamine stimulation. A mechanism for irradiation erythema

Journal of Clinical Investigation, 1990

Acute ultraviolet light B (UVB) injury is associated with dermal mast cell histamine release. The possibility that histamine-stimulated prostaglandin (PG) synthesis could be a mechanism for irradiation erythema was therefore examined using human skin explants. Explants responded to UV irradiation (120 mJ/cm2) with a fivefold increase in synthesis of prostaglandins E2, F2 alpha and 6-keto PGF1 alpha. Incubating explants with the H1 antihistamines brompheniramine (50 microM) or pyrilamine (30 microM) inhibited PG release from irradiated explants 63 +/-4.9% (mean +/-SEM) 6 h after UV exposure. Antihistamines did not affect PG synthesis in control explants. Irradiation increased the histamine concentration in explant conditioned medium only 50% over basal values, suggesting that irradiation enhanced histamine responsiveness. Explants were therefore incubated with exogenous histamine. In irradiated explants, PG synthesis was stimulated threefold by 3 microM histamine. Unirradiated explants' PG synthesis was unaffected by histamine. Enhanced histamine sensitivity was also examined in epidermal cell cultures. In irradiated cultures, histamine sensitivity was again markedly potentiated: as little as 1 microM histamine stimulated significant PGE2 release and the response to 10-30 microM histamine was increased six to eight times compared with that of unirradiated cultures. These studies demonstrate that endogenous histamine stimulates PG synthesis in human skin after UV injury by potentiation of histamine-induced prostaglandin release. Potentiated agonist responses induced by UV exposure may […]

Ultraviolet radiation and the skin immune response

ACTA CLINICA …, 2003

At present, ultraviolet radiation (UVR) represents one of the most important environmental factors affecting mankind. Besides the beneficial effects of UVR such as vitamin D production, it is known that UVR can lead to adverse effects on human health. The best known harmful effects are sunburns, tumors of the skin and ocular damage. It is noteworthy that UVR effects are not restricted to skin-associated infections, as there is strong evidence for their association with systemic (non-skin-associated) infections as well. Alterations in immune functions that are induced by UVR are initiated by the absorption of light energy by chromophores and their transformation into photoproducts. Some of them are removed by repair mechanisms, others induce signal transduction pathways, whereas some exhibit cytotoxicity. The observable skin response may occur within minutes of light exposure (e.g. urticaria) or may take days (e.g. inhibition of contact hypersensitivity), or much longer periods to be expressed (e.g. tumors). Today, artificial UVR (phototherapy) is used in dermatology for induction of immunomodulation in many forms of autoimmune and/or hyperimmune responses in the skin.

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