Mice exposure to repetitive low UV doses differentially affects the immune system compared to elevated doses, enhancing specific antibody production.

ELIANA CELA; MARIELA PAZ; ADRIAN FRIEDRICH; JULIANA LEONI; DANIEL GONZALEZ MAGLIO

Edimburgo

Congreso; International Investigative Dermatology; 2013

International Investigative Dermatology

Mice exposure to repetitive low UV doses differentially affects the immune system compared to elevated doses, enhancing specific antibody production. E. M. Cela1, M. L. Paz1, A. D. Friedrich1, J. Leoni1, D. H. Gonzalez Maglio1 1. Immunology, Pharmacy and Biochemistry School, University of Buenos Aires, Buenos Aires, Argentina. Skin UV exposure induces both a systemic immunesuppression and Vitamin D synthesis, which in turns promotes transcription of immune mediators such as antimicrobial peptides and TLR-2. SKH-1 hairless mice were irradiated with repetitive low UV doses (4 times of 20 mJ/cm2 -simulating daily exposure-) or a single high dose (400 mJ/cm2 ?simulating harmful exposure-) to compare their cellular as well as immune effects, 1 and 8 days post-UV. Both UV doses led to an increase in epidermal thickness& (H&E), but only 4x20 activated mitochondrial function# (DiOC6+ cells) while 1x400 produced the opposite effect&, with the consequent increment in superoxide production# (MitoSOX+ cells), by flow cytometry. Inflammatory mediators (IL-6 and TNF-α) were increased only in 1x400, in dermis& and epidermis& extracts, assayed by ELISA. Epidermal T cell percentage (CD3+ cells) was markedly decreased in 1x400# (flow cytometry); accordingly, epidermal transcription of CXCL-12 was also decreased&, but in all mice groups& (RT-PCR). Both UV doses induced an increment in VEGF transcription, in dermis and epidermis#, but none of them had effects on the transcription of TLR-2 and TLR-4, in both tissues (RT-PCR), or in the 25-OH-Vit D serum levels (RIA). Finally, a tetanus toxoid (TT) challenge was performed for each UV-dose 1 or 8d after irradiation and serum antibodies were titrated. Anti-TT specific total IgG# and IgG3# were increased 1d post-4x20 (3.4 and 3.5 fold), while anti-TT IgG1& and IgG2b* were decreased 1d post-1x400 (3.0 and 4.6 fold). Immunizations performed 8d after-UV did not have effects on specific antibodies titre, in neither group. All differences are expressed vs non-irradiated control mice: *p<0.05, #p<0.01, &p<0.001. Simulated daily UV-exposure shares some of the negative effects produced by a harmful high-dose, in contrast it does not induce strong inflammation and it is also unexpectedly capable of increasing the specific humoral immune response.