[Inhibitory effect of iguratimod on TNFalpha production and NF-kappaB activity in LPS-stimulated rat alveolar macrophage cell line].
OBJECTIVE
To investigate the effect of iguratimod (T-614), a non-steroidal anti-inflammatory drug, on TNFalpha mRNA expression and TNFalpha production, and on the activity of nuclear factor-kappaB (NF-kappaB) in the rat alveolar macrophage cell line (NR8383) activated by LPS.


METHODS
NR8383 cells were pretreated with T-614 (13.4, 26.7, 53.4 micromol x L(-1)), then were stimulated with LPS. The production of TNFalpha in the supernatant of NR8383 was assayed by enzyme-linked immunosorbent assay (ELISA). The TNFalpha mRNA level was determined by a semi-quantitative PCR assay. Assessment of the NF-kappaB DNA binding activity was performed by an ELISA kit.


RESULTS
T-614 inhibited LPS-stimulated mRNA expression and production of TNFalpha in a concentration-dependent manner, as well as the activity of NF-kappaB. The IC50 value of effect of T-614 on TNFalpha level was 26.2 micromol x L(-1).


CONCLUSIONS
The inhibitory effect of T-614 on the production of TNFalpha in LPS-stimulated NR8383 cells may be mediated by suppression of NF-kappaB activity.
Jiang
Ye
Y
Center for New Drug Research and Development, Jiangsu Key Laboratory for Molecular Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing 210097, China.
Lü
Wei
W
Yu
Shu-Qin
SQ
Yao
Lin
L
Xu
Guang-Lin
GL
Zhang
Xi-Ran
XR
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology*; D008070:Lipopolysaccharides; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002867:Chromones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; C519076:iguratimod