Interferon α2b increases MMP-13 and IL-10 expression in Kupffer cells through MAPK signaling pathways.

Abstract

Background/aims: Kupffer cells play critical roles in both progression and resolution of liver fibrosis. Interferon α2b is an important immunoregulator which has anti-fibrotic effect in addition to its antiviral effect. It remained unclear whether the anti-fibrotic effect of interferon α2b is mediated by regulating functions of Kupffer cells.

Methodology: Primary isolated Kupffer cells were cultured with interferon α2b and the expression of matrix metalloproteinase-13, interleukin-10, transforming growth factor -β1 and tumor necrosis factor-α were measured. To investigate the role of mitogen-activated protein kinase pathways in regulating cytokines production by interferon α2b-stimulated Kupffer cells, inhibitors were given before cells were treated with interferon a2b.

Results: Cell purity was more than 98%. Stimulating Kupffer cells with interferon α2b led to a dramatic increase in matrix metalloproteinase-13 and interleukin-10 expression. In contrast, the values of tumor necrosis factor-α and transforming growth factor -β1 remained unchanged throughout the 24-hour observation period. Inhibited ERK1/2 pathway prevented interferon α2b-triggered matrix metalloproteinase-13 production, while inhibited p38MAPK, ERK1/2 or JNK signaling pathways all blocked interleukin-10 expression.

Conclusions: Interferon α2b may exert anti-fibrotic effect by elevating the level of matrix metalloproteinase-13 and interleukin-10 in Kupffer cells, in a mitogen-activated protein kinase signaling pathways-dependent manner.