Abstract
Exposure to high dose radiation causes radiation injury. There are many reports that radiation activates the production of tumor necrosis factor α (TNFα) in various cells. TNFα is also thought to be a pro-inflammaroty cytokine and this factor plays a critical role in the initiation and continuation of inflammation and immunity. The excess production of TNFα leads to damage of organs. However, the roles of endogenously produced TNFα are not fully understood in radiation exposure. Using TNFα knock-out mice (TNFα-/-), we investigated the role of TNFα in radiation-induced apoptosis of intestine of mice treated with lipopolysaccharide (LPS). Whole body irradiation with 10 Gy induced apoptosis in intestine of TNFα+/+ and TNFα-/-, but no difference of the magnitude in apoptosis was observed in both mice. The level of TNFα in serum was not detectable even in TNFα-/- mice. TNFα and LPS are known as radioprotectors. Pre-treatment with either recombinant TNFα or LPS enhanced radiation-induced apoptosis in TNFα-/-, although these factors inhibited apoptosis in TNFα+/+ mice. The level of TNFα in serum was increased following to TNFα challenge, but there was no differnce of the levels between TNFα+/+ and TNFα-/- mice. On the other hand, administrations of LPS increased the serum levels of TNFα, IL-1α and IL-1β in TNFα+/+, but not in TNFα-/- mice. These results suggest that endogenously produced TNFα is not related to radiation-induced intestinal apoptosis, but may be essential for LPS-induced cytokine productions that can be associated with intestinal apoptosis.
