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Immunomodulating Agents in Gastrointestinal Disease
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
Samir A. Shah, Athos Bousvaros, A. Christopher Stevens
Corticosteroids are potent inhibitors of the inflammatory response and immunomodulators via multiple nonspecific mechanisms. These mechanisms include inhibiting arachidonic acid release from cell membranes, cytokine release by immune cells, chemotaxis, and phagocytosis [63,64]. Corticosteroids inhibit interleukin 2 transcription and mRNA production by preventing association of the AP-1 transcription factor with its corresponding binding site on the lymphocyte’s interleukin 2 promoter [65]. Glucocorticoids have also recently been shown to stimulate the production of IκBα, which binds to NF-κB, trapping it in the cytosol [66,67]. NF-κB can activate many immunoregulatory genes in response to proinflammatory stimuli by translocating into the nucleus and acting as a transcription factor for these cytokine genes. Thus, inhibition of NF-κB activity by steroids may account for their multiple antiinflammatory effects.
Aesthetic
Published in Tor Wo Chiu, Stone’s Plastic Surgery Facts, 2018
Retin-A (tretinoin) increases keratinocyte turnover and thins the stratum corneum but thickens the dermis with increased collagen synthesis and elasticity. It binds to DNA receptors that bind to activator protein-1 (AP-1) transcription factor, leading to inhibition of metalloproteinase action.
Reduction and Fixation of Sacroiliac joint Dislocation by the Combined Use of S1 Pedicle Screws and an Iliac Rod
Published in Kai-Uwe Lewandrowski, Donald L. Wise, Debra J. Trantolo, Michael J. Yaszemski, Augustus A. White, Advances in Spinal Fusion, 2003
Kai-Uwe Lewandrowski, Donald L. Wise, Debra J. Trantolo, Michael J. Yaszemski, Augustus A. White
Nuclear crosstalk of the ERK/Smad pathway is also possible given the number of common nuclear targets. One such target is fos of the AP-1 transcription factor. Fos is phosphorylated by ERK on sites that have been identified as transcriptional inhibitors [32,33], but it is also a functional target of the Smad 3 MH2 domain, which ultimately potentiates transcription of genes
In silico identification and biological evaluation of a selective MAP4K4 inhibitor against pancreatic cancer
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Chao-Di Chang, Min-Wu Chao, Hsueh-Yun Lee, Yi-Ting Liu, Huang-Ju Tu, Ssu-Ting Lien, Tony Eight Lin, Tzu-Ying Sung, Shih-Chung Yen, Sing-Han Huang, Kai-Cheng Hsu, Shiow-Lin Pan
MAP4K4 regulates biological behaviours in many malignancies by phosphorylating MKK4. Phosphorylation of MKK4 on S257 and T261 by MAP4K4 would further enhance the JNK phosphorylation20. Phosphorylated MKK4 directly phosphorylates JNK on T183 and Y185 to activate the JNK signalling pathway21,22. JNK has a common substrate site at the C-terminus and a glutamate aspartate domain at the N-terminus that interacts with MKK423. JNK can phosphorylate c-Jun, which then forms a heterodimer with c-Fos, known as the activator protein-1 (AP-1) transcription factor24. The AP-1 transcription factor then enters the cell nucleus to translate proteins related to cell apoptosis, cell survival, the proliferation of mitogens (e.g., MMPs and VEGF), and system inflammation22,25,26. Recent studies indicated that JNK signalling pathway regulates cell survival in response to proinflammatory cytokines and growth factors, which are essential in cancer development25,27. In summary, MAP4K4 and its role in regulating the JNK signalling pathway mediate many proliferation-related functions to promote cancer development. Therefore, identifying novel MAP4K4 inhibitors with potency and high selectivity is important to suppress JNK-induced proliferation and cell growth.
Curcumin analog, GO-Y078, induces HO-1 transactivation-mediated apoptotic cell death of oral cancer cells by triggering MAPK pathways and AP-1 DNA-binding activity
Published in Expert Opinion on Therapeutic Targets, 2022
Ming-Hsien Chien, Pei-Chun Shih, Yi-Fang Ding, Li-Hsin Chen, Feng-Koo Hsieh, Meng-Ying Tsai, Pei-Yi Li, Chiao-Wen Lin, Shun-Fa Yang
It was reported that induction of HO-1 expression is mediated through cis-regulatory DNA sequences located in its promoter region. Several AP-1-binding sites were shown to be involved in the transcriptional induction of HO-1 by MAPKs and the polyphenol CUR or quercetin [53,54]. The AP-1 transcription factor is a dimer of Jun and Fos family proteins. In our study, we found that transcriptional activity of AP-1 was induced by GO-Y078 in OSCC cells. We actually observed that GO-Y078 treatment significantly increased the binding activities of c-Jun and c-Fos on the promoter region of the HMOX1 gene. These results suggest that GO-Y078 mediates transcriptional induction of HO-1 via targeting AP-1 in OSCC cells. In addition to AP-1, nuclear factor-erythroid 2-related factor 2 (Nrf2) is an another TF which can form a heterodimer with the small Maf protein and then bind to the antioxidant response element (ARE) of HMOX1 to regulate HO-1 expression. Actually, it was reported that HO-1 expression induced by CUR also requires activation of the Nrf2/ARE pathway [55]. In addition to transcriptional regulation of HMOX1 by CUR, epigenetic modulation is also involved in CUR-regulated HMOX1 expression through inhibiting histone deacetylase 2 (HDAC2) [40]. Whether the HDAC2 and Nrf2/ARE pathways are involved in GO-Y078-induced upregulation of HMOX1 in OSCC cells needs to be further investigated in the future.
Minor variant of AHSG gene 767C>G polymorphism may decrease the risk of gestational diabetes mellitus
Published in Journal of Obstetrics and Gynaecology, 2020
Halit Akbas, Suna Kahraman, Sibel Sak, Feridun Akkafa
The second polymorphism we researched in our study is the –843A>T (rs2248690) polymorphism in the 5’UTR region of the AHSG gene. Inoue et al. reported that this polymorphism affects the transcriptional activity of the gene by altering the association of the gene with the AP-1 transcription factor (Inoue et al. 2008). Lehtinen et al. reported that some polymorphisms, including rs2248690 (–843A>T) in the AHSG gene, were associated with the level of coronary artery calcification in diabetic patients (Lehtinen et al. 2007). Jensen et al. asserted that rs2248690 polymorphism was not associated with type 2 diabetes (Jensen et al. 2013). According to the results of our study, it is noteworthy that the homozygous TT genotype, which is a polymorphic variant of the gene has never been seen in the patients with GDM. While in the control group, it was seen just in four individuals. However, this result was not statistically significant when compared between the patient and the control group. The low allele frequency of this polymorphism in our study group (0.11 ± 0.02) led to the conclusion that the selected sample size was not sufficient to substantiate the findings of this polymorphism. In the subsequent studies, we think that stronger statistical results regarding this polymorphism can be obtained by increasing the sample size of study group.