INHIBITORY EFFECT OF INTERLEUKIN-13 ON NUCLEAR FACTOR-KAPPA B ACTIVATION
IN HUMAN MESANGIAL CELLS
Zhang Ai-H, Chen R-H, Ding G-X
Nanjing Medical University, Nanjing, China
Objective: Nuclear factor-kappa B
(NF-kB) is one of
the most inportant proinflammatory transcription factors and plays a major
role in the induced expression of genes involved in cellular proliferation
and inflammatory response. IL-13 is known to suppress the expression of
inflammatory cytokines in human mesangial cells (HMC), but the mechanism of
which is not known. The aims of this study were: (1) to define the
mechanism of NF-kB
activation in HMC; (2) to determine whether IL-13 inhibits activation of
NF-kB in these
cells.
Methods: Cultured HMC were
stimulated with LPS, IL-1b, TNF-a, and angiotensin II (Ang II) in the presense and absense of
pretreatment of IL-13. Electrophoretic mobility shift assay (EMSA) and
Western Blot were used to detect the activity of NF-kB and degradation of IkB.
Results: EMSA showed that constitute
activation of NF-kB was
observed in unstimulated HMC and LPS, IL-1b, TNF-a, and
Ang II significantly activated NF-kB in
HMC. Supershift assay demonstrated that p65 and p50 were the predominant
subunits involved. Pretreatment of HMC with IL-13 block LPS-induced NF-kB activation, nuclear translocation of p65 subunit, and
degradation of IkBa and IkBb. IL-13 also inhibited NF-kB activation by IL-1b,
TNF-a, and Ang
II.
Conclusion: These
results suggested that IL-13 is a potent inhibitor of actvation of NF-kB in HMC, which may contribute to its previously described
anti-inflammatoy effects.