UVB radiation-mediated inhibition of contact hypersensitivity reactions is dependent on the platelet-activating factor system.
Through its ability to both induce immunosuppression and act as a carcinogen, UVB radiation plays a major role in cutaneous malignancies. Recent studies have indicated that UVB-mediated inhibition of delayed-type hypersensitivity reactions is mediated, in part, by the lipid mediator platelet-activating factor (PAF). The objective of this study was to further define the mechanism by which UVB inhibits contact hypersensitivity (CHS) reactions. UVB irradiation resulted in an inhibition of subsequent CHS to the chemical DNFB in wild-type, but not in PAF-R-deficient mice. UVB-mediated inhibition of CHS was also blocked by a cyclooxygenase-2 (COX-2) inhibitor or a neutralizing antibody directed against IL-10. UVB irradiation upregulated IL-10 mRNA levels in lymph nodes and spleen only to significant levels in PAF-R-expressing mice. Bone marrow transplantation studies demonstrated that UVB-mediated immunomodulatory effects were dependent on PAF-R-positive bone marrow. These studies suggest that UVB irradiation results in epidermal production of PAF agonists, which then act on PAF-R-positive bone marrow-derived cells to upregulate IL-10 through COX-2-generated prostaglandins.
Zhang
Qiwei
Q
Department of Dermatology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Yao
Yongxue
Y
Konger
Raymond L
RL
Sinn
Anthony L
AL
Cai
Shanbao
S
Pollok
Karen E
KE
Travers
Jeffrey B
JB
D000818:Animals; D051546:Cyclooxygenase 2 / Q000502:physiology; D003877:Dermatitis, Contact / Q000276:immunology / Q000517:prevention & control*; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010972:Platelet Activating Factor / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D014466:Ultraviolet Rays
D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D016753:Interleukin-10; D051546:Cyclooxygenase 2