In the murine macrophage cell line RAW264. 7, hemin was selleckchem Imatinib found to attenuate LPS induced NFB activation. Silencing HO 1 was found to enhance LPS induced nuclear factor Inhibitors,Modulators,Libraries B activation suggesting an inhibitory role of HO 1 on NFB activa tion which is also required downstream for NO production. Thus, hemin could also inhibit IL 1b stimulated downstream NFB activation in astrocytes. Our demonstration that SnPP blocks hemin suppressed IL 1b induced inflammatory TNF a and CXCL10 pro duction in human astrocytes corresponds well with the finding that overexpression of HO 1 inhibited LPS induced TNF and IL 1b expression in THP 1 cells, providing further evidence for the anti inflammatory effect of HO 1. Several caveats and limitations in our study must be acknowledged.

The constitutive expression of HO 2 in our human primary astrocytes may also have contribu ted to the inhibition of NO as shown by non selective SnPP treatment on IL 1b. Another possible explanation is that SnPP alters an unknown mechan ism leading Inhibitors,Modulators,Libraries to the enhancement of IL 1b induced iNOS expression and NO production in astrocytes. Although there was no cytotoxicity detected by either MTT or alamarBlue assays, we observed that hemin treatment altered astrocyte morphology to a smaller cell size without changing b actin expression. We also observed minor inhibition of GFAP expression by hemin. Hemin induced HO 1 expression was observed in about 50% of astrocytes. this could be due to sub types of andor delayed response among astrocytes in cultures.

Transfection of astrocytes with an HO 1 expression vector demonstrated the Inhibitors,Modulators,Libraries inhibitory effect of HO 1 on iNOS, but potential mechanisms involving byproducts from the HO reaction, i. e. CO, iron, bili verdin and bilirubin, should not be ignored. In conclusion, we have demonstrated in vitro the robust induction of HO 1 expression in human astro cytes exposed to hemin. Induced HO 1 expression exerts an inhibitory Inhibitors,Modulators,Libraries effect on iNOS expression and NO production in IL 1b stimulated human astrocytes and the inhibitory effects of hemin are mediated mainly through HO 1 induction and associated with reduced activation of p38 MAPK. Extrapolation of these in vitro human brain cell culture results to in vivo models should be undertaken with caution as there are species and response differences to be expected.

However, these findings support the concept that HO 1 expression in astrocytes is an antioxidant defense system in the face of neuroinflammation. Background Asthma is a result of pathological airway inflammation. Inhibitors,Modulators,Libraries Infiltrating inflammatory cells release mediators that contribute to manifestations ref 1 of the disease. Importantly, these mediators cause activation of the stress system, which co ordinates adaptive responses of the organism to stressors, maintaining basal and stress related home ostasis.