The IL-6R α chain controls lung CD4+CD25+ Treg development and function during allergic airway inflammation in vivo
J. Clin. Invest. Aysefa Doganci, et al. 115:313 doi:10.1172/JCI22433 [
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Figure 2Local blockade of sIL-6R by gp130-Fc downregulates IL-4, IL-5, and IL-13 levels and reduces GATA-3 expression in experimental asthma. BALB/c mice were sensitized and challenged with OVA whereas control mice were given saline. Some OVA-sensitized mice received additional treatment with gp130-Fc to block sIL-6R function in vivo, as indicated. gp130-Fc treatment was associated with a significant decrease in IL-4 (
A), IL-5 (
B), and IL-13 (
C) levels in BALF of OVA-sensitized mice. *
P < 0.05; **
P < 0.01; ***
P < 0.001. Data represent mean values ± SEM from 5 mice per group. (
D) Total lung proteins were isolated from gp130-Fc–treated mice and untreated control mice at day 28 and analyzed by Western blot analysis after immunoblotting with a monoclonal antibody directed against GATA-3. Furthermore, ERK2 expression was determined on the same blot after membrane stripping and incubation with an anti–ERK-2 antibody. Each lane in the Western blot was loaded with 50 μg proteins isolated from different mice (saline,
n = 4; OVA,
n = 5; OVA + gp130-Fc,
n = 5). Quantification of Western blots by densitometry is reported in
E and shows decreased GATA-3 expression after i.n. delivery of gp130-Fc in OVA-sensitized and -challenged mice (*
P < 0.05; ***
P = 0.00056). (
F) RT-PCR for GATA-3 and T-bet in 10
5 lung CD4
+ T cells per group after total RNA extraction. Both anti–IL-6R antibody and gp130-Fc treatment led to upregulation of T-bet, while GATA-3 remained unchanged in lung OVA-specific CD4
+ T cells.