Anti-inflammatory effects of UV-irradiated lymphocytes: induction of IL-1Ra upon phagocytosis by monocyte/macrophages.
One of the mechanisms proposed to explain immunomodulatory actions of ultraviolet light (UV) is production of endogenous anti-inflammatory cytokines. The purpose of the present study is to evaluate how UV light affects the production of IL-10 and IL-1Ra and to provide insight as to the role of phagocytosis of apoptotic lymphocytes in this process. Cytokine production was evaluated in a coculture system consisting in UV-treated lymphocytes in the presence of autologous PBMC. The impact of phagocytosis was tested by two blocking agents cytochalasin E and anti-CD36 mAb. The apoptotic process affecting irradiated lymphocytes was progressive, culminating at 48 h. To achieve significant cytokine production, irradiated lymphocytes were incubated overnight at 37 degrees C. Coculture of apoptotic lymphocytes with autologous PBMC resulted in a significant increase of IL-1Ra mRNA (+340%; P = 0.001) and protein (+72%; P = 0.001) production. This synthesis was blocked by cytochalasin E but upregulated by CD36 receptor cross-linking. Our study shows that UV light induces lymphocyte apoptosis followed by its phagocytosis by monocyte/macrophages, a step that preferentially activates IL-1Ra.
Craciun
Ligia I
LI
Department of Immunology, Haematology and Transfusion, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik, 808, 1070 Brussels, Belgium.
DiGiambattista
Mario
M
Schandené
Liliane
L
Laub
Ruth
R
Goldman
Michel
M
Dupont
Etienne
E
D017209:Apoptosis / Q000528:radiation effects; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007700:Kinetics; D008214:Lymphocytes / Q000528:radiation effects*; D008264:Macrophages / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology*; D012795:Sialoglycoproteins / Q000378:metabolism*; D014466:Ultraviolet Rays
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D012795:Sialoglycoproteins