TGFb modulation of MIPla expression in human fetal microglia

Microglial cells play an important regulatory role in inflammatory diseases of the central nervous system (CNS), such as multiple sclerosis. Monocyte chemoattractants have been shown to be expressed in the CNS of animal models of multiple sclerosis. As the regulation of these chemoattractants may be key to the progression of the neuroimmunologic diseases, we analyzed expression of MIPla in human fetal microglial cultures. The cells express minimal levels of MIPla, but when treated with LPS(10ng/ml) MIPla message and protein is induced in a dose and time dependent manner. Pretreatment of cultures with TGFb (10ng/ml) downmodulates this expression at both the message and protein level. Similarly, cotreatment with TGFb (10ng/ml) and LPS (10ng/ml) appears to reduce MIPla expression when compared to treatment with LPS alone. These results indicate that TGFb may function to decrease chemoattraction of inflammatory cells to the site of injury in neuroimmunologic diseases.