p(HGNC:STAT3)
Downstream from the nicotine-stimulated kinases, a number of transcription factors have been shown to be activated. Among these factors are the cAMP response element binding protein (CREB) and the activating transcription factor 2 (ATF-2) in PC12 cells (211, 337, 460), the Ets-like transcription factor Elk-1 in the rat hippocampus (349), and the signal transducer and activator of transcription (STAT3) in macrophages and skin cells (114, 354). PubMed:19126755
JAK-2, another early target in the nicotine neuroprotection pathway that may mediate signaling between the nAChR and the PI3K pathway (Shaw et al., 2002), may link nAChR activation with the JAK/signal transducer and activator of transcription 3 (STAT-3) protective pathway. JAK-2 is also activated by nicotine in non-neuronal cells such as nAChR-bearing keratinocytes (Arredondo et al., 2006). In a microarray study, expression of 8 of 33 JAK/STAT pathway genes was altered when human bronchial epithelial cells were exposed to 5 microM nicotine for 4 to 10 h (Tsai et al., 2006). Thus, the JAK-2/STAT-3 pathway is activated by exposure to nicotine. PubMed:19293145
Paradoxically, Abeta also activates the MAPK pathway through an alpha7-dependent pathway (Dineley et al., 2001; Bell et al., 2004). In human oral keratinocytes, the Ras/Raf/mitogen-activated protein kinase kinase 1/ERK pathway cooperates with the nicotine activation of the JAK/STAT-3 pathway (Arredondo et al., 2006); the Ras pathway induces STAT-3 upregulation whereas the JAK/STAT-3 pathway phosphorylates STAT-3. PubMed:19293145
JAK-2, another early target in the nicotine neuroprotection pathway that may mediate signaling between the nAChR and the PI3K pathway (Shaw et al., 2002), may link nAChR activation with the JAK/signal transducer and activator of transcription 3 (STAT-3) protective pathway. JAK-2 is also activated by nicotine in non-neuronal cells such as nAChR-bearing keratinocytes (Arredondo et al., 2006). In a microarray study, expression of 8 of 33 JAK/STAT pathway genes was altered when human bronchial epithelial cells were exposed to 5 microM nicotine for 4 to 10 h (Tsai et al., 2006). Thus, the JAK-2/STAT-3 pathway is activated by exposure to nicotine. PubMed:19293145
We have shown previously that anatabine displays some anti-inflammatory properties by reducing the activation of NFκB and STAT3 [17,18]. PubMed:26010758
We have previously shown that anatabine inhibits STAT3 and NFκB activation [18] resulting in decreased neuroinflammation in a mouse model of multiple sclerosis. PubMed:26010758
A significant reduction in STAT3 phosphorylation was observed in the hippocampus and cortex of Tg PS1/APPswe mice treated with 10 or 20 mg/Kg/Day of anatabine compared to Tg PS1/APPswe receiving regular drinking water (Fig 6B) showing that anatabine prevents STAT3 activation in the brain of Tg PS1/APPswe mice. PubMed:26010758
NF-κB positively regulates the transcription of interleukin 6 (IL6) family of cytokines such as IL6, leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) [184], which in-turn induce the differentiation of NSC into astrocytes by activating transcription factors STAT3, AP-1, and NF-κB itself PubMed:28745240
NF-κB positively regulates the transcription of interleukin 6 (IL6) family of cytokines such as IL6, leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) [184], which in-turn induce the differentiation of NSC into astrocytes by activating transcription factors STAT3, AP-1, and NF-κB itself PubMed:28745240
NF-κB positively regulates the transcription of interleukin 6 (IL6) family of cytokines such as IL6, leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) [184], which in-turn induce the differentiation of NSC into astrocytes by activating transcription factors STAT3, AP-1, and NF-κB itself PubMed:28745240
JAK-2, another early target in the nicotine neuroprotection pathway that may mediate signaling between the nAChR and the PI3K pathway (Shaw et al., 2002), may link nAChR activation with the JAK/signal transducer and activator of transcription 3 (STAT-3) protective pathway. JAK-2 is also activated by nicotine in non-neuronal cells such as nAChR-bearing keratinocytes (Arredondo et al., 2006). In a microarray study, expression of 8 of 33 JAK/STAT pathway genes was altered when human bronchial epithelial cells were exposed to 5 microM nicotine for 4 to 10 h (Tsai et al., 2006). Thus, the JAK-2/STAT-3 pathway is activated by exposure to nicotine. PubMed:19293145
JAK-2, another early target in the nicotine neuroprotection pathway that may mediate signaling between the nAChR and the PI3K pathway (Shaw et al., 2002), may link nAChR activation with the JAK/signal transducer and activator of transcription 3 (STAT-3) protective pathway. JAK-2 is also activated by nicotine in non-neuronal cells such as nAChR-bearing keratinocytes (Arredondo et al., 2006). In a microarray study, expression of 8 of 33 JAK/STAT pathway genes was altered when human bronchial epithelial cells were exposed to 5 microM nicotine for 4 to 10 h (Tsai et al., 2006). Thus, the JAK-2/STAT-3 pathway is activated by exposure to nicotine. PubMed:19293145
Conversely, repression is effected by signal transducer and activator of transcrip- tion 3 (STAT3) and possibly zinc-finger protein with KRAB and SCAN domains 3 (ZKSCAN3), although its role has been disputed 22,32 . PubMed:30116051
In these cells, basal expression of YKL-40 is RelB-, p65-, and STAT3-independent, implicating other unknown factors. PubMed:25681350
NF-κB positively regulates the transcription of interleukin 6 (IL6) family of cytokines such as IL6, leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) [184], which in-turn induce the differentiation of NSC into astrocytes by activating transcription factors STAT3, AP-1, and NF-κB itself PubMed:28745240
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.