International Journal of Immunopharmacology
Prevention of ultraviolet radiation-induced suppression of contact hypersensitivity by Aloe vera gel components
Introduction
Exposure to UVB (280–320 nm) has been shown to generate an immunosuppressive microenvironment in the skin. UVB irradiated skin was unable to elicit sensitization to contact allergens, but rather induced tolerance to them (Toews et al., 1980, Elmet et al., 1983). UVB irradiated skin was also unable to reject syngeneic UVB-induced tumors, although the same tumors were strongly rejected when transplanted into non-UVB-exposed syngeneic mice (Kripke, 1984).
Local immunosuppression by UVB radiation appears to be closely related to damages of epidermal LC, which are accessory cells delivering costimulatory signals as well as antigens to T cells (Streilein, Grammar, Yoshikawa, Demiden, & Bermeer, 1990). UVB radiation was shown to abrogate the accessory cell function of LC (Stingl et al., 1981, Austaad and Braathen, 1985, Cruz et al., 1989, Simon et al., 1991), probably through distortion or deletion of costimulatory molecules such as ICAM-1 from LC (Krutmann et al., 1990, Tang and Udey, 1992aa). Functional inactivation of costimulatory signals by UVB radiation would result in conversion of the function of LC from immunogenic to tolerogenic (Simon, Krutmann, Elmets, Bergstresser, & Cruz, 1992). In higher doses, UVB radiation was shown to exert more severe toxic activity for LC leading ultimately to elimination (Bergstresser et al., 1980, Lynch et al., 1981, Tang and Udey, 1992bb).
An immunomodulator that prevents UVB-irradiated LC from functional alteration or elimination would reduce some of the immunosuppressive effects of UVB in the skin. Such an immunomodulator would be invaluable in preventing UVB-induced immune suppression in the skin, because currently used sunscreens such as para-aminobenzoate (Padimate) and 2-ethylhexyl-p-methoxycinnamate (2-EHMC) were shown to be unable to reduce local immune suppression, although they could reduce sunlight-induced erythema (Mommaas et al., 1990, Ho et al., 1992).
To search for an immunomodulator that prevents UVB-induced functional alteration of LC, we developed an in vitro screening system (Lee et al., 1997). Briefly, freshly isolated murine epidermal LC were irradiated with UVB (180 J/m2), and then cultured in a cell culture medium containing the sample(s) to be tested for 2 days. Accessory cell function of the UVB-irradiated and then sample-treated LC was measured by assessing their ability to support anti-CD3 monoclonal antibody-primed T cell mitogenesis. With this in vitro functional assay method, we identified and purified UVB-protective immunomodulators from the gel of Aloe vera (Lee et al., 1997). The activity-guided sequential fractionation of the gel of Aloe vera showed that it contains at least two small molecular weight immunomodulators that prevent UVB-induced suppression of LC accessory cell function in vitro. In the present study we evaluated the UVB-protective activity of the immunomodulators in vivo.
Section snippets
Mice
Specific pathogen-free male C57BL/6 mice were purchased from Korea Research Institute of Chemical Technology (Daejeon, Korea), and used between 8–14 weeks of age.
Isolation of Aloe component, G1C2F1
The Aloe component, G1C2F1, was isolated from the gel of Aloe vera as described previously (Lee et al., 1997). Briefly, the lyophilized Aloe vera gel, provided from The Aloe Research Foundation (Fort Worth, Tx, USA), was dissolved in distilled water, and then fractionated according to the molecular size. Components in the range of
Determination of UVB dose
To determine optimal dose of UVB radiation to suppress CHS response to TNCB, the shaved ventral skin was exposed to different doses of a single UVB radiation, rested for 3 days, and then painted with TNCB. Six days later, right ears of the mice were challenged with TNCB. The CHS response is illustrated by the net ear swelling (Fig. 1). Exposure to a single UVB radiation suppressed CHS response in a dose dependent manner reaching plateau of suppression at around 3.0 KJ/m2 of UVB radiation (some
Discussion
Previously, we reported that Aloe vera gel contains small molecular weight immunomodulators, G1C1F1, that restore UVB-suppressed accessory cell function of epidermal LC in vitro (Lee et al., 1997). In the present study we evaluated the UVB-protective activity in vivo. In evaluating the UVB-protective activity in CHS model in mice, we decided to induce local immune suppression by a single radiation exposure instead of several daily radiation exposures. The irradiated skin was then treated
References (21)
- et al.
Natural and perturbed distributions of Langerhans cells: Responses to ultraviolet light, heterotopic skin grafting, and dinitrofluorobenzene sensitization
Journal of Investigative Dermatology
(1980) - et al.
Disparate effects of in vitro low-dose UVB irradiation on intravenous immunization with purified epidermal cell subpopulations for induction of contact hypersensitivity
Journal of Investigative Dermatology
(1989) - et al.
Sunscreens protect epidermal Langerhans cells and Thy-1+cells but not local contact sensitization from the effects of ultraviolet light
Journal of Investigative Dermatology
(1992) - et al.
Prevention of ultraviolet radiation-induced suppression of accessory cell function of Langerhans cells by Aloe vera gel components
Immunopharmacology
(1997) - et al.
Analysis of the protective effects of topical sunscreens on the UVB-radiation-induced suppression of the mixed lymphocyte reaction
Journal of Investigative Dermatology
(1990) - et al.
Prevention of ultraviolet radiation-induced suppression of contact and delayed hypersensitivity by Aloe barbadensis gel extract
Journal of Investigative Dermatology
(1994) - et al.
Effects of ultraviolet radiation on murine Langerhans cells: Doses of ultraviolet radiation that modulate ICAM-1(CD54) expression and inhibit Langerhans cell function cause delayed cytotoxicity in vitro
Journal of Investigative Dermatology
(1992) - et al.
Effects of UVB on alloactive and antigen presenting capacity of human epidermal Langerhans cells
Scandinavian Journal of Immunology
(1985) - et al.
Analysis of the mechanism of unresponsiveness produced by haptens painted on the skin exposed to low dose ultraviolet radiation
Journal of Experimental Medicine
(1983) Immunological unresponsiveness induced by UV radiation
Immunological Reviews
(1984)