In:
Journal of Pineal Research, Wiley, Vol. 55, No. 3 ( 2013-10), p. 294-303
Abstract:
Aberrant expression of inducible nitric oxide synthase (i NOS ) in macrophages, which has been reported to be suppressed by melatonin, has an important contribution in the development of pathological inflammation. Visfatin, an adipokine, regulates the expression of various inflammatory factors, leading to inflammation; however, the influence of visfatin on i NOS ‐driven processes in macrophages is unclear. Here, we report the assessment of the role of visfatin in the regulation of i NOS gene expression in macrophages. Our data show that the levels of i NOS protein in peritoneal macrophages as well as nitric oxide ( NO ) in blood plasma were significantly lower after lipopolysaccharide treatment in visfatin +/− mice than those in the WT mice. In addition, visfatin increases i NOS m RNA and protein levels in RAW 264.7 cells, along with increasing production of NO . The enhancement of i NOS expression was prevented by treating the cells with inhibitors of the Janus kinase 2/signal transducers and activators of transcription 3 ( JAK 2/ STAT 3), nuclear factor ( NF )‐κ B , extracellular signal–regulated kinase 1/2, and c‐ J un N ‐terminal kinase pathways. Our results also show that visfatin‐induced i NOS expression and NO production were significantly inhibited by melatonin, an effect that was closely associated with a reduction in phosphorylated JAK 2/ STAT 3 levels and with the inhibition of p65 translocation into nucleus. In conclusion, our data show, for the first time, that melatonin suppresses visfatin‐induced i NOS upregulation in macrophages by inhibiting the STAT 3 and NF ‐κ B pathways. Moreover, our data suggest that melatonin could be therapeutically useful for attenuating the development of visfatin–i NOS axis‐associated diseases.
Type of Medium:
Online Resource
ISSN:
0742-3098
,
1600-079X
DOI:
10.1111/jpi.2013.55.issue-3
Language:
English
Publisher:
Wiley
Publication Date:
2013
detail.hit.zdb_id:
632697-3
detail.hit.zdb_id:
2027992-9
