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IL-4 stimulates mouse macrophages to express APRIL through p38MAPK and two different downstream molecules, CREB and
Young-Saeng Jang1, Hyun-A Kim, Seok-Rae Park
1Department of Molecular Bioscience, School of Bioscience and Biotechnology, Kangwon National University, Chuncheon 200-701, South Korea.
Abstract:
APRIL (a proliferation-inducing ligand) is primarily expressed by macrophages and dendritic cells, and has profound effects on B cell physiology. In this study, we investigated the role of IL-4 in APRIL expression by mouse macrophages and the signaling mechanism involved. IL-4 markedly enhanced APRIL expression in mouse macrophages at the transcriptional and protein level. The p38MAPK inhibitor SB203580 completely abolished the IL-4 effect, whereas overexpression of CREB with IL-4 augmented APRIL expression. This increase was abolished by SB203580 treatment, indicating that p38MAPK may activate CREB. Overexpression of Stat6 also augmented IL-4-induced APRIL expression; this effect was partially abolished by SB203580 but not by the Jak inhibitor AG490, indicating that Stat6 mediates IL-4-induced APRIL expression in a Jak-independent manner and that p38MAPK acts as the intermediate. Our results demonstrate that IL-4 up-regulates APRIL expression through two divergent pathways in mouse macrophages, p38MAPK-CREB and p38MAPK-Stat6.
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