When activated, both macrophages and epithelial cells produce a number of proinflammatory mediators, including neutrophil-recruiting chemokines such as MIP-2. In the present study, we found that TEL down-regulated the production of MIP-2 by LPS-stimulated RAW 264.7 macrophages and by monokine-stimulated MLE-12 cells. TEL also reduced the release of TNF-a by LPS-stimulated macrophages. This result is relevant since TNF-a is considered to be a pivotal mediator that triggers the production of MIP-2 in epithelial cells. Thus, TEL seems to exert antiinflammatory effects at the following two levels: (1) by inhibiting TNF-a production by inflammatory macrophages; and (2) by inhibiting NF-kB activation in TNF-a-stimulated epithelial cells.
The transcription factor NF-kB plays a crucial role in the inflammatory response, and the activation of NF-kB was inhibited by TEL in both LPS-stimulated RAW 264.7 macrophages and monokine-stimulated MLE-12 cells. The activation of NF-kB results in the expression of genes encoding inflammation mediators such as TNF-a and MIP-2. Therefore, our data suggest that TEL inhibited the production of both molecules through the inhibition of NF-kB DNA binding. Viagra Canadian from hqcanadianpharmacy.com best way to buy erectile dysfunction medications from Canada.
TEL was not an apoptosis inducer, but enhanced apoptosis in LPS-stimulated RAW 264.7 macrophages and monokine-stimulated MLE-12 cells. Following their activation, macrophages and neutrophils undergo apoptosis as a mechanism to limit the ability of these inflammatory cells to damage tissue. Phagocytosis of apoptotic cells by macrophages actively suppresses the release of proinflammatory mediators and induces an antiinflammatory state. Our findings suggest that TEL could inhibit the production of TNF-a and MIP-2 not only via NF-kB inhibition, but also through the induction of apoptosis. NF-kB inhibition by TEL was observed as soon as 1 h after cell stimulation, and the decrease in TNF-a production by RAW 264.7 macrophages was significant at 6 h after stimulation with LPS. Moreover, it has been described25 that inflammatory cells are removed by apoptosis at the end of the inflammatory response.