The effect of exendin-4 on vital activity, nitric oxide and TNF-α production of murine peritoneal macrophages

Glucagon like peptide 1 (GLP-1) is a peptide released from the small intestine and mainly enhances glucose-induced insulin secretion, although its receptor (GLP-1R) is distributed on various cells including mice and human macrophages. Regarding important functions of macrophage in regulating pro-inflammatory and immune responses, in this study, the effect of exendin-4 (an analog of GLP-1) on vital activity, nitric oxide and TNF-α production of peritoneal macrophages was investigated.
Peritoneal macrophages were isolated from C57BL/6 mice and cultured with or without LPS for 24 hours and 0.03 to 3 nM exendin-4. The vital activity was evaluated by MTT, nitrite by Griess method and TNF-α by ELISA.
Exendin-4 at 3 and 0.3 nM significantly reduced MTT of macrophages (resting), but increased it in stimulated macrophages at 3 nM. Exendin-4 at 0.3 and 0.03 nM reduced nitrite in resting macrophages, although it (3 nM) induced an increase in LPS stimulated macrophages. An increase in TNF-α production of and resting (3 nM) and stimulated macrophages (1 and 3 nM) was also observed.
The effect of exendin-4 on nitrite and TNF production of macrophages in vitro is dependent on the cell status of activation (besides its concentration) and it may function as pro- or anti-inflammatory.