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Whole-Body Fluorescence Imaging in Cancer Research
Published in Margarida M. Barroso, Xavier Intes, In Vivo, 2020
Marina V. Shirmanova, Diana V. Yuzhakova, Maria M. Lukina, Alena I. Gavrina, Aleksandra V. Meleshina, Ilya V. Turchin, Elena V. Zagaynova
Cancer studies with the use of fluorescent proteins are generally performed on human tumor xenografts transplanted into immunodeficient mice. However, the development of tumor therapies based on the activation of antitumor immunity requires highly immunogenic tumor models growing in the immunocompetent animals. It is known that fluorescent proteins, such as GFP, EGFP, and KillerRed, possess such immunogenic properties (Stripecke et al., 1999; Steinbauer et al., 2003; Castano et al., 2006; Yuzhakova et al., 2015). In a study of the therapeutic effects of the soluble OX40 ligand (OX40L), we used EGFP-expressing murine colon cancer transplanted to BALB/c mice and obtained an effective tumor rejection and the development of immunological memory in the treated animals (Serebrovskaya et al., 2016). In our tumor model, the OX40L was genetically encoded in the cancer cells and coexpressed with EGFP; therefore, fluorescence imaging of the tumors enabled not only monitoring of the tumor regression but also the intravital control of OX40L production. Figure 21.5 illustrates the regression of a tumor coexpressing EGFP and OX40L and the progression of tumors expressing EGFP alone.
Topical application of celastrol alleviates atopic dermatitis symptoms mediated through the regulation of thymic stromal lymphopoietin and group 2 innate lymphoid cells
Published in Journal of Toxicology and Environmental Health, Part A, 2021
Jae Kwon Lee, Jin Kyung Seok, Ilyoung Cho, Gabsik Yang, Kyu-Bong Kim, Seung Jun Kwack, Han Chang Kang, Yong-Yeon Cho, Hye Suk Lee, Joo Young Lee
Thymic stromal lymphopoietin (TSLP) is expressed by dermal epithelial cells that stimulate Th2 differentiation to initiate Th2 immune responses (He et al. 2008). The expression of TSLP is involved in the pathogenesis of various diseases including atopic dermatitis, asthma, and inflammatory arthritis (Ebner et al. 2007; Yang et al. 2018; Ying et al. 2005). TSLP expression levels are up-regulated in atopic dermatitis patients skin lesions (Soumelis et al. 2002). In atopic dermatitis, TSLP is produced by skin keratinocytes in response to external stimuli such as allergens, cytokines, viruses, bacteria and fungi, and plays an important role in early development of diseases (Ziegler 2012). Increased TSLP levels stimulate immature dendritic cells to express OX40 ligand in an antigen-specific manner (Gilliet et al. 2003). The expression of OX40 ligand-dendritic cells promotes the differentiation of naïve CD4 T cells into Th2 cells (Ohshima et al. 1997). TSLP also directly stimulates development of naïve CD4 T cells or CD8 T cells into Th2 cells. The activation of TSLP receptor (TSLPR) initiates IL-4 gene transcription, which induces positive feedback to upregulate the TSLPR located on CD4 T cells (Omori and Ziegler 2007). It is noteworthy that Th2 cells produce increased Th2 cytokines levels of IL-4, IL-5, and IL-13 (Leyva-Castillo et al. 2013). Th2 cytokines lead to elevated IgE production by inducing class switching in B cells, and skin inflammatory responses, exacerbating skin barrier defects in atopic dermatitis (Guttman-Yassky and Krueger 2017). Therefore, TSLP expression is considered a hallmark of early pathogenesis of atopic dermatitis (Wang et al. 2013).