Methods: STZ-diabetic rats were administered daily by oral gavage CMC 2.24 (30mg/kg) for 3 weeks. At sacrifice, thioglycolate-elicited peritoneal macrophages were collected from the peritoneal cavity and isolated from the peritoneal fluid by density gradient centrifugation & incubated in cell culture in the presence or absence of P. gingivalis endotoxin (LPS). Cytokine and MMP-9 levels in the conditioned media were analyzed by ELISA and gelatin zymography; Cell chemotactic activity was analyzed as well.
Results: The untreated diabetic rats produced the greatest number of peritoneal macrophages in vivo and the highest levels of cytokines IL-1β, IL-6 and MMP-9 in cell culture. CMC 2.24 treatment reduced the excessive accumulation of macrophages in peritoneal exudates in vivo. Our results showed that CMC 2.24 not only inhibits inflammatory mediators (IL-1β, IL-6 and MMP-9), but also restores diabetes induced impaired cell function (chemotaxis) without affecting the severity of diabetes assessed by blood glucose levels.
Conclusions: In this study, we demonstrated that orally administered CMC 2.24 significantly prevented excessive accumulation of peritoneal macrophages in diabetic rats; normalized the levels of cytokines and MMP-9 produced by macrophages; and restored the impaired cell function. This compound may effectively treat chronic inflammatory diseases by improving the “competence” of inflammatory cells (e.g. macrophages), thus reducing the abnormal tissue destruction and resolving the inflammatory response.
Supported by NYSTAR grant #A43273 from CAT, SBU, Chem-Master Intl., Inc., and SB-Summer-Research-Fellowship-Program.