The regulation of polyunsaturated fatty acids (PUFAs) on macrophage migration inhibitory factor (MIF) in THP-1 macrophages
2012
Hochschulschrift
Zugriff:
100
Macrophage migration inhibitory factor (MIF) is an important pro-inflammatory cytokine and has presumed a vital role as a upstream regulator of host antimicrobial responses. Macrophages act as sentinel cells in the innate immune system. They play roles in destroying pathogens and releasing substances that act on other immune cells. MIF lacks an amino-terminal leader sequence, indicating that it is secreted from cells by a non-classical secretion pathway. Literatures report that MIF is implicated in the pathogenesis of sepsis and inflammatory diseases, suggesting that MIF might offer a therapeutic target for human diseases. Animal experiments and clinical studies demonstrate that n-3 polyunsaturated fatty acids (n-3 PUFAs) might also have the therapeutic effect on anti-inflammation. In this study, THP-1 macrophages were pretreated with docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) for 24 hours before stimulation with LPS. The results showed that DHA and EPA inhibited LPS-induced MIF secretion, but these two n-3 PUFAs had no effect on the mRNA and protein levels of MIF. Immunoprecipitation analysis showed that LPS induced the interaction between MIF and ABCA1 which participates in MIF secretion pathway, and pretreatment of DHA and EPA suppressed the interaction. Furthermore, DHA and EPA repressed the colocalization of MIF and ABCA1 induced by LPS. SQ 22536, an inhibitor of protein kinase A (PKA), reversed the LPS-induced MIF secretion. Moreover, the interaction of MIF and ABCA1 was reduced in THP-1 macrophages pretreated with the PKA inhibitor in immunoprecipitation experiment. Thus, we suggest that LPS stimulates MIF secretion via activation of PKA signaling pathway. In conclusion, Our data reveal that DHA and EPA may inhibit LPS-induced MIF secretion by modulating the molecules involved in MIF secretion pathway and supply a novel insight to the mechanisms of n-3 PUFAs on anti-inflammation.
Titel: |
The regulation of polyunsaturated fatty acids (PUFAs) on macrophage migration inhibitory factor (MIF) in THP-1 macrophages
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Autor/in / Beteiligte Person: | Kao, Yung-Ling ; 高咏菱 |
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Veröffentlichung: | 2012 |
Medientyp: | Hochschulschrift |
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