Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 52 (12), 695-699

Transduced Tat-CIAPIN1 Reduces the Inflammatory Response on LPS- And TPA-induced Damages

Affiliations

Transduced Tat-CIAPIN1 Reduces the Inflammatory Response on LPS- And TPA-induced Damages

Hyeon Ji Yeo et al. BMB Rep.

Abstract

Cytokine-induced apoptosis inhibitor 1 (CIAPIN1), known as an anti-apoptotic and signal-transduction protein, plays a pivotal role in a variety of biological processes. However, the role of CIAPIN1 in inflammation is unclear. We investigated the protective effects of CIAPIN1 in lipopolysaccharide (LPS)-exposed Raw 264.7 cells and against inflammatory damage induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in a mouse model using cell-permeable Tat-CIAPIN1. Transduced Tat-CIAPIN1 significantly reduced ROS production and DNA fragmentation in LPS-exposed Raw 264.7 cells. Also, Tat-CIAPIN1 inhibited MAPKs and NF-κB activation, reduced the expression of Bax, and cleaved caspase-3, COX-2, iNOS, IL-6, and TNF-α in LPS-exposed cells. In a TPA-induced animal model, transduced Tat-CIAPIN1 drastically decreased inflammation damage and inhibited COX-2, iNOS, IL-6, and TNF-α expression. Therefore, these findings suggest that Tat-CIAPIN1 might lead to a new strategy for the treatment of inflammatory skin disorders. [BMB Reports 2019; 52(12): 695-699].

Conflict of interest statement

CONFLICTS OF INTEREST

The authors have no conflicting interests.

Figures

Fig. 1
Fig. 1
Effects of transduced Tat-CIAPIN1 protein on LPS-induced ROS production and DNA fragmentation. The localization of transduced Tat-CIAPIN1 protein was examined by confocal fluorescence microscopy (A). Scale bar = 20 μm. Cells were treated with Tat-CIAPIN1 (3 μM) or CIAPIN1 protein for 1 h before treatment with 1 μg/ml of LPS for 3 h or 14 h. Then, intracellular ROS levels (B) and DNA fragmentation (C) were measured by DCF-DA staining and TUNEL staining. Fluorescence intensity was quantified using an ELISA plate reader. Scale bar = 50 μm. *P < 0.05, compared with LPS-treated cells.
Fig. 2
Fig. 2
Effects of Tat-CIAPIN1 protein on LPS-induced inflammatory responses in Raw 264.7 cells. The cells were treated with Tat-CIAPIN1 (3 μM) or CIAPIN1 protein for 1 h before being exposed to LPS (1 μg/ml). MAPK and NF-κB activation (A) and the expression levels of COX-2 (B) and iNOS (C) protein were analyzed by Western blotting. Total RNA was extracted from the cells. We analyzed cytokines (IL-6 and TNF-α) and GAPDH mRNA by RT-PCR using specific indicated primers (D). The band intensity was measured by densitometer. *P < 0.05, compared with LPS-treated cells.
Fig. 3
Fig. 3
Effects of Tat-CIAPIN1 protein on TPA-induced mice ear edema. Ears of mice were treated with TPA (1 μg/ear) once a day for 3 days. Tat-CIAPIN1 protein (10 μg) was topically applied to the mouse ears 1 h prior to TPA exposure over 3 days. Protective effects of Tat-CIAPIN1 protein were confirmed by hematoxylin and eosin staining, changes in ear weight, and ear thickness in a TPA-induced mice ear edema model. Scale bar = 50 μm. *P < 0.05, compared with TPA-treated mice.
Fig. 4
Fig. 4
Effects of Tat-CIAPIN1 protein on TPA-induced pro-inflammatory mediator protein (iNOS and COX-2) and cytokine (IL-6 and TNF-α) expression in mice ears. Mice were stimulated with TPA (1 μg/ear), after which Tat-CIAPIN1 protein (10 μg) was topically applied to the mouse ears for 3 days. Mouse ear extracts were prepared. After total RNA was extracted from ear biopsies, pro-inflammatory mediator proteins (iNOS and COX-2) and cytokine (IL-6 and TNF-α) expression levels were measured by RT-PCR using specific primers (A, B). The expression levels of pro-inflammatory mediator protein (iNOS and COX-2) were confirmed by Western blotting (C, D). The band intensity was measured by densitometer. *P < 0.05, compared with TPA-treated mice.

Similar articles

See all similar articles

References

    1. Fan G, Jiang X, Wu X, et al. Anti-inflammatory activity of Tanshinone IIA in LPS-stimulated RAW264.7 macrophages via miRNAs and TLR4-NF-kappaB pathway. Inflammation. 2016;39:375–384. doi: 10.1007/s10753-015-0259-1. - DOI - PubMed
    1. Duffield JS. The inflammatory macrophage: a story of Jekyll and Hyde. Clin Sci. 2003;104:27–38. doi: 10.1042/cs1040027. - DOI - PubMed
    1. Fujihara M, Muroi M, Tanamoto K, Suzuki T, Azuma H, Ikeda H. Molecular mechanisms of macrophage activation and deactivation by lipopolysaccharide: roles of the receptor complex. Pharmacol Ther. 2003;100:171–194. doi: 10.1016/j.pharmthera.2003.08.003. - DOI - PubMed
    1. Chung HY, Cesari M, Anton S, et al. Molecular inflammation as an underlying mechanism of aging: the anti-inflammatory action of calorie restriction. Ageing Res Rev. 2009;8:18–30. doi: 10.1016/j.arr.2008.07.002. - DOI - PMC - PubMed
    1. Korhonen R, Lahti A, Kankaanranta H, Moilanen E. Nitric oxide production and signaling in inflammation. Curr Drug Targets Inflamm Allergy. 2005;4:471–479. doi: 10.2174/1568010054526359. - DOI - PubMed
Feedback