Regulation of TNF - alpha Gene Expression in Human Fetal Astrocytes

Tumor necrosis factor-n (TNF - alpha) involved in the pathogenesis of multiple sclerosis and contribute to the degeneration of oligodendrocytes as well as neurons. TNF - alpha is produced by miocroglia and astrocytes, which also produce hormones and cytokines that influence its biological activity. Astrocytes, the major glial cells in the CNS, are capable of producing TNF - alpha at both the mRNA and protein levels in response to interleukine-1 (IL-1) or TNF - alpha. Two immunosuppressive cytokines, transforming growth factor - beta (TGF - beta) and IL-10, have been shown to influence glial cell function. TGF - beta can modulate the activity of glial cells by inhibiting interferon-gamma (IFN - gamma) induced expression of class II major histocompatibility complex (MHC) molecules on astrocytes and microglia. To explore the role of astrocytes in the production of TNF - alpha, astrocytes were pretreated with IL-10 or TGF - beta and then stimulated with IL-1p to determine their effects on TNF - alpha production. The secretion of TNF - alpha by human fetal astrocytes was markedly inhibited by TGF - beta at a low concentration. In contrast IL-10 had no effect on TNF - alpha mRNA level. These results show that TGF - beta may regulate the expression of TNF - alpha in activated human fetal astrocytes.

IL - 5 and IL - 10 production of peripheral blood mononuclear cells by stimulation of D. farinae antigen in atopic asthmatics / 천식및알레르기

BACKGROUND: IL - 5 has been recognized as a potent proeosinophilic cytokine and IL-10 has been reported as an important anti - inflammatory cytokine in allergic inflammation. But the clinical roles of these cytokines in allergic asthma are still unclear. Objectives : We studied the clinical implications of IL - 5 and IL - 10 secretions from stimulated peripheral blood mononuclear cells ( PBMC ) in Dermatophagoides farinae ( DF ) atopic asthmatics ( BA ). METHODS: Thirty - six DF sensitized BA and 9 non - atopic BA were enrolled for this study. Twenty - seven out of 36 subjects were challenged by inhalation of DF crude allergen. The isolated PBMCs were cultured for 6 days with DF antigen and the stimulatory index ( SI ) and secretions of IL - 5, IFN - y and IL - 10 from PBMC were measured. We analyzed these parameters with clinical parameters. RESULTS: SI (4.2 +/- 1.0 vs. 1.3 +/- 0.3, p<0.05) and secretions of IL - 5 ( 19.9 vs. 1.7 g/L, p< 0.001 ) and IL-10 ( 185.5 vs. 34.3 g/L, p(0.05 ) from the atopic BA were significantly higher than those of non-atopic BA, but the secretion of IFN - r was not different between the two groups ( 56.6 vs. 47.3 ug/L ). No significant difference in secretions of IL - 5, IL - 10, IFN - r and SI of PBMC was found between responder and non - responder of DF inhalation challenge test. Among responders to antigen challenge test ( n = 17 ), the production of IL - 5 correlated with the productions of IL - 10 (r = 0.773, p< 0.01 ) and methacholine PC20 ( r = 0.503, p< 0.05 ). Production of IL - 5 from the PBMC of atopic mild intermittent BA ( n = 10 ) was higher than that of atopic per'sistent BA ( n = 27 ) ( p< 0.01 ), but no difference in IL - 10, IFN - r and SI was found between the two groups. Conclusions : Allergen specific productions of IL - 5 and IL - 10 from the PBMC may be specific for atopic subjects and secretion of IL - 5 from the stimulated PBMC may contribute to the pathogenesis of atopic BA. The severity of BA may be more influenced by other factors.