ABSTRACT
<p><b>OBJECTIVE</b>The purpose of the present study was to observe the changes in CD4+CD25+Nrp1+Treg cells after irradiation with different doses and explore the possible molecular mechanisms involved.</p><p><b>METHODS</b>ICR mice and mouse lymphoma cell line (EL-4 cells) was used. The expressions of CD4, CD25, Nrp1, calcineurin and PKC-α were detected by flow cytometry. The expressions of TGF-β1, IL-10, PKA and cAMP were estimated with ELISA.</p><p><b>RESULTS</b>At 12 h after irradiation, the expression of Nrp1 increased significantly in 4.0 Gy group, compared with sham-irradiation group (P<0.05) in the spleen and thymus, respectively, when ICR mice received whole-body irradiation (WBI). Meanwhile the synthesis of Interleukin 10 (IL-10) and transforming growth factor-β1 (TGF-β1) increased significantly after high dose irradiation (HDR) (> or = 1.0 Gy). In addition, the expression of cAMP and PKA protein increased, while PKC-α, calcineurin decreased at 12h in thymus cells after 4.0 Gy X-irradiation. While TGF-β1 was clearly inhibited when the PLC-PIP2 signal pathway was stimulated or the cAMP-PKA signal pathway was blocked after 4.0 Gy X-irradiation, this did not limit the up-regulation of CD4+CD25+Nrp1+Treg cells after ionizing radiation.</p><p><b>CONCLUSION</b>These results indicated that HDR might induce CD4+CD25+Nrp1+Treg cells production and stimulate TGF-β1 secretion by regulating signal molecules in mice.</p>
Subject(s)
Animals , Female , Male , Mice , Calcineurin , Genetics , Metabolism , Cyclic AMP , Metabolism , Dose-Response Relationship, Radiation , Gene Expression Regulation , Radiation Effects , Immunosuppression Therapy , Interleukin-10 , Genetics , Metabolism , Lymphocyte Subsets , Physiology , Neuropilin-1 , Genetics , Metabolism , Phosphoinositide Phospholipase C , Genetics , Metabolism , Protein Kinases , Genetics , Metabolism , Signal Transduction , Transforming Growth Factor beta , Genetics , Metabolism , Whole-Body IrradiationABSTRACT
<p><b>OBJECTIVE</b>Since most reports on bystander effect have been only concerned with radiation-induced damage, the present paper aimed at disclosing whether low dose radiation could induce a stimulatory or beneficial bystander effect.</p><p><b>METHODS</b>A co-culture system containing irradiated antigen presenting cells (J774A.1) and unirradiated T lymphocytes (EL-4) was established to observe the effect of J774A.1 cells exposed to both low and high doses of X-rays on the unirradiated EL-4 cells. Incorporation of 3H-TdR was used to assess the proliferation of the EL-4 cells, expression of CD80/86 and CD48 on J774A.1 cells was measured with immunohistochemistry and flow cytometry, respectively. NO release from J774A.1 cells was estimated with nitrate reduction method.</p><p><b>RESULTS</b>Low dose-irradiated J774A.1 cells could stimulate the proliferation of the unirradiated EL-4 cells while the high dose-irradiated J774A.1 cells exerted an inhibitory effect on the proliferation of the unirradiated EL-4 cells. Preliminary mechanistic studies illustrated that the differential changes in CD48 expression and NO production by the irradiated J774A.1 cells after high and low dose radiation might be important factors underlying the differential bystander effect elicited by different doses of radiation.</p><p><b>CONCLUSION</b>Stimulatory bystander effect can be induced in immune cells by low dose radiation.</p>