Ionizing Radiation Induces Cytokines, MMP-1, TIMP-1 and Supresses Type I Collagen mRNA Expressions in Human Gingival Fibroblasts

Abstract

We aimed to evaluate the effects of ionizing radiation on the proliferation of gingival fibroblasts and the expressions of proinflammatory cytokines and matrix metalloproteinase-1 (MMP-1), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and type I collagen (type I Col) mRNA transcripts. Gingival fibroblasts were treated with radiation doses as follows; 0.5 Gy, 1 Gy, 2 Gy, 4 Gy, 6 Gy, and 8 Gy. Expression of interleukin (IL)-1s, IL-6, IL-8 and, MMP-1, TIMP-1 and of type I Col mRNA transcripts in human gingival fibroblasts was determined by quantitative polymerase chain reaction (PCR) analysis. Morphology of gingival fibroblasts was evaluated using inverted microscope. Ionizing radiation decreased cell proliferation (p< 0.05) compared to the control group. Expressions of IL-1 s, IL-6 and IL-8 were stimulated at the highest dosage of radiation (p< 0.001). In parallel to proinflammtory cytokines, MMP-1 and TIMP-1 mRNA expressions were elevated in response to higher dosage of radiation (p< 0.001). Radiation suppressed type I Col mRNA expression in response to all doses at 24 hrs (p< 0.001). In addition to basal epithelial cells of the oral mucosa, gingival fibroblasts have an important role in the pathogenesis of oral mucositis. Results of this study may help to clarify the role of gingival fibroblasts in radiation induced oral mucositis.