scholarly journals LPS Cooperates with Poly-L-Arginine to Promote IL-6 and IL-8 Release via the JNK Signaling Pathway in NCI-H292 Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Ling-Ling Zhang ◽  
Bing Chen ◽  
Xiao-Yun Fan ◽  
Sha-Sha Wu ◽  
Sheng-Quan Zhang ◽  
...  
Keyword(s):  
Synergistic Effect ◽  
Signaling Pathway ◽  
Enzyme Linked Immunosorbent Assay ◽  
Jnk Pathway ◽  
Jnk Signaling ◽  
Time Points ◽  
Phosphorylation Level ◽  
Combined Use ◽  
Jnk Signaling Pathway ◽  
Lps Treatment

Objective. Herein, we aimed to study the mechanism whereby poly-L-arginine (PLA) and lipopolysaccharide (LPS) can synergistically induce the release of interleukin-6 (IL-6) and IL-8 in NCI-H292 cells.Methods. NCI-H292 cells were divided into control, PLA, LPS, and PLA+LPS groups. At various time points, the phosphorylation of JNK in each group was measured by western blotting. Additionally, the productions of IL-6 and IL-8 were assessed using an enzyme-linked immunosorbent assay (ELISA). The effects of SP600125, an inhibitor of the JNK pathway, on the increase of p-JNK, IL-6, and IL-8 were also studied.Results. Our results showed that either PLA or LPS treatment alone can significantly increase the phosphorylation level of JNK in NCI-H292 cells. Of interest was the combined use of PLA and LPS that has a synergistic effect on the phosphorylation of JNK, as well as synergistically inducing the release of IL-6 and IL-8 in NCI-H292 cells. Furthermore, SP600125 significantly inhibited the activation of JNK signal, as well as reducing the productions of IL-6 and IL-8 in response to PLA+LPS stimulation.Conclusions. The JNK signaling pathway contributes to the release of IL-6 and IL-8, which is stimulated by the synergistic actions of PLA+LPS in NCI-H292 cells.

scholarly journals hCG Improves Luteal Function and Promotes Progesterone Output through the Activation of JNK Pathway in the Luteal Granulosa Cells of the Stimulated IVF Cycles†

2020 ◽  
Vol 102 (6) ◽  
pp. 1270-1280 ◽  
Author(s):  
Gamze Bildik ◽  
Nazli Akin ◽  
Yashar Esmaeilian ◽  
Francesko Hela ◽  
Kayhan Yakin ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Signaling Pathway ◽  
Granulosa Cells ◽  
Luteal Phase ◽  
Steroidogenic Enzymes ◽  
Jnk Pathway ◽  
Jnk Signaling ◽  
Luteal Function ◽  
Jnk Signaling Pathway

Abstract Human chorionic gonadotropin (hCG) is a luteotropic hormone that promotes the survival and steroidogenic activity of corpus luteum (CL) by acting through luteinizing hormone receptors (LHRs) expressed on luteinized theca and granulosa cells (GCs). Therefore, it is used to support luteal phase in in vitro fertilization (IVF) cycles to improve clinical pregnancy rates and prevent miscarriage. However, the molecular mechanism underlying this action of hCG is not well characterized. To address this question, we designed an in vitro translational research study on the luteal GCs obtained from 58 IVF patients. hCG treatment at different concentrations and time points activated c-Jun N-terminal kinase (JNK) pathway and significantly increased its endogenous kinase activity along with upregulated expression of steroidogenic enzymes (steroidogenic acute regulatory protein (stAR), 3β-Hydroxysteroid dehydrogenase (3β-HSD)) in a dose-dependent manner in the luteal GCs. As a result, in vitro P production of the cells was significantly enhanced after hCG. When JNK pathway was inhibited pharmacologically or knocked-down with small interfering RNA luteal function was compromised, P4 production was declined along with the expression of stAR and 3β-HSD in the cells. Further, hCG treatment after JNK inhibition failed to correct the luteal defect and promote P4 output. Similar to hCG, luteinizing hormone (LH) treatment improved luteal function as well and this action of LH was associated with JNK activation in the luteal GCs. These findings could be important from the perspective of CL biology and luteal phase in human because we for the first time identify a critical role for JNK signaling pathway downstream LHR activation by hCG/LH in luteal GCs. Summary Sentence JNK signaling pathway plays a central role in the upregulated expression of the steroidogenic enzymes StAR and 3b-HSD and augmented progesterone production by hCG/LH in human luteal granulosa cells.

Effect of pharmacologic inhibition of c-Jun N-terminal kinase (JNK) signaling pathway on cell proliferation and cell cycle progression in human granulosa cell tumor.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22004-e22004
Author(s):  
Ozgur Oktem ◽  
Meltem Muftuoglu ◽  
Filiz Senbabaoglu ◽  
Bulent Urman
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Granulosa Cell ◽  
Dependent Manner ◽  
Jnk Pathway ◽  
Jnk Signaling ◽  
Curative Therapy ◽  
Jnk Signaling Pathway ◽  
Dose Dependent

e22004 Background: No data are available regarding the signaling pathways that controls the proliferation of granulosa cell tumors (GCT). Preliminary findings showing the activation of c-Jun N-terminal kinase (JNK) signaling pathway in the proliferating granulosa cells has led us to investigate the role of this pathway in human GCT. Methods: Human GCT line COV 434 was used. Cell proliferation was monitored real-time quantitatively for 120h using an impedance-based system. Two different pharmacologic JNK inhibitors SP600125 and AS601245 were used. Their inhibitory concentrations were determined in western blot. Cell cycle was analyzed with flow cytometry and apoptosis with yo-pro-1 staining. Results: First, the growth characteristics of this cell line was delineated (Table 1A). Then the cells were treated with the inhibitors at the indicated doses during the log phase. Their proliferation was significantly halted in a dose-dependent manner by both inhibitors (Table 1B). Furthermore, the cells failed to complete mitosis, and began to accumulate at G2 in a dose dependent manner when JNK pathway was interrupted with AS601245 (59%) and SP600125 (39%) during G2/M transition compared to control cells (7%) proceeding through G2/M phase regularly (p<0.001). Compared to 3.5% of control cells, 14% and 30% of the cells underwent apoptosis when treated with 50 µM SP600125 and AS601245, respectively. At 100 µM, the apoptotic fraction increased to 68% and 76%, respectively (p<0.01). Conclusions: These results suggest that pharmacologic manipulation of JNK pathway may provide a therapeutic benefit in the treatment of GCT for which currently, no curative therapy exists beyond surgery. Funded by a Grant to Ozgur Oktem (TUBITAK109S164). [Table: see text]

scholarly journals Terminal differentiation of human granulosa cells as luteinization is reversed by activin-A through silencing of Jnk pathway

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Gamze Bildik ◽  
Nazli Akin ◽  
Yashar Esmaeilian ◽  
Francesko Hela ◽  
Ceren Sultan Yildiz ◽  
...  
Keyword(s):  
Corpus Luteum ◽  
Signaling Pathway ◽  
Granulosa Cells ◽  
Molecular Mechanisms ◽  
Terminal Differentiation ◽  
Reproductive Technologies ◽  
Activin A ◽  
Jnk Pathway ◽  
Jnk Signaling ◽  
Jnk Signaling Pathway

Abstract Molecular mechanisms underlying luteinization (terminal differentiation of granulosa and theca cells after ovulation) and luteolysis (demise of corpus luteum) are poorly understood in human ovary. Here we report that activin-A, after binding to its cognate receptors induces a functional luteolytic state and reverses luteinization phenotype by downregulating the expression of the steroidogenic enzymes, LH receptor and VEGF and reducing estradiol (E2) progesterone (P4) production and upregulating FSH receptor and cyclin D1 expression in human primary luteinized granulosa cells. Further, this action of activin-A involves downregulation of JNK signaling pathway and is opposite to that of human chorionic gonadotropin (hCG), which acts as a luteotropic hormone and improves luteal function through the activation of JNK pathway in the same cell type. Reversal of luteinization phenotype in luteal granulosa cells by activin-A potentially makes this hormone an attractive candidate for use under certain clinical situations, where induction of luteolysis and rapid reduction of endogenous sex steroid levels are beneficial such as ovarian hyperstimulation syndrome (OHSS), in which the ovaries hyper-respond to gonadotropin stimulation by producing too many growing follicles along with development of ascites, pleural effusion, and hemo-concentrations as a result of increased vascular permeability and leakage of intravascular volume into third spaces. Our work unveils a previously undefined role for activin-A and JNK signaling pathway in human corpus luteum biology, that might have a direct clinical impact in assisted reproductive technologies.

scholarly journals Suppression of ischemia in arterial occlusive disease by JNK-promoted native collateral artery development

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Kasmir Ramo ◽  
Koichi Sugamura ◽  
Siobhan Craige ◽  
John F Keaney ◽  
Roger J Davis
Keyword(s):  
Blood Flow ◽  
Signaling Pathway ◽  
Arterial Occlusion ◽  
Arterial Occlusive Disease ◽  
Occlusive Disease ◽  
Artery Ligation ◽  
Jnk Pathway ◽  
Jnk Signaling ◽  
Collateral Arteries ◽  
Jnk Signaling Pathway

Arterial occlusive diseases are major causes of morbidity and mortality. Blood flow to the affected tissue must be restored quickly if viability and function are to be preserved. We report that disruption of the mixed-lineage protein kinase (MLK) - cJun NH2-terminal kinase (JNK) signaling pathway in endothelial cells causes severe blockade of blood flow and failure to recover in the murine femoral artery ligation model of hindlimb ischemia. We show that the MLK-JNK pathway is required for the formation of native collateral arteries that can restore circulation following arterial occlusion. Disruption of the MLK-JNK pathway causes decreased Dll4/Notch signaling, excessive sprouting angiogenesis, and defects in developmental vascular morphogenesis. Our analysis demonstrates that the MLK-JNK signaling pathway is a key regulatory mechanism that protects against ischemia in arterial occlusive disease.

scholarly journals The cJUN NH2-terminal kinase (JNK) signaling pathway promotes genome stability and prevents tumor initiation

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Nomeda Girnius ◽  
Yvonne JK Edwards ◽  
David S Garlick ◽  
Roger J Davis
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Tumor Formation ◽  
Driver Mutations ◽  
Tumor Initiation ◽  
Loss Of Function ◽  
Jnk Pathway ◽  
Jnk Signaling ◽  
Promote Cell Proliferation ◽  
Jnk Signaling Pathway

Breast cancer is the most commonly diagnosed malignancy in women. Analysis of breast cancer genomic DNA indicates frequent loss-of-function mutations in components of the cJUN NH2-terminal kinase (JNK) signaling pathway. Since JNK signaling can promote cell proliferation by activating the AP1 transcription factor, this apparent association of reduced JNK signaling with tumor development was unexpected. We examined the effect of JNK deficiency in the murine breast epithelium. Loss of JNK signaling caused genomic instability and the development of breast cancer. Moreover, JNK deficiency caused widespread early neoplasia and rapid tumor formation in a murine model of breast cancer. This tumor suppressive function was not mediated by a role of JNK in the growth of established tumors, but by a requirement of JNK to prevent tumor initiation. Together, these data identify JNK pathway defects as ‘driver’ mutations that promote genome instability and tumor initiation.

Association of Ras-Raf-MEK-Erk/JNK pathway mutations with overall survival for lung squamous cell carcinoma patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14754-e14754
Author(s):  
Long Xu ◽  
Ming Liu ◽  
Tanxiao Huang ◽  
Suo Peisu ◽  
Lele Song ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Lung Squamous Cell Carcinoma ◽  
Rank Test ◽  
Jnk Pathway ◽  
Jnk Signaling ◽  
Log Rank Test ◽  
Jnk Signaling Pathway

e14754 Background: Genomic alterations often lead to aberrant signaling pathways which play an important role in tumorigenesis and development. Here we report the mutational status of genes associated with the Ras-Raf-MEK-Erk/JNK signaling pathway as a biomarker for predicting overall survival (OS) for Lung squamous cell carcinoma (SQCC) patients. Methods: We used the cBioPortal platform to analyze a cohort of 494 SQCC samples from TCGA data. The general Ras-Raf-MEK-Erk/JNK signaling pathway includes 26 genes (KRAS, HRAS, BRAF, RAF1, MAP3K1, MAP3K2, MAP3K3, MAP3K4, MAP3K5, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K5, MAPK1, MAPK3, MAPK4, MAPK6, MAPK7, MAPK8, MAPK9, MAPK12, MAPK14, DAB2, RASSF1, RAB25). We analyzed the number of samples with/without mutations in the Ras-Raf-MEK-Erk/JNK pathway and found is 214 and 284 that had, or didn’t have, mutations in this pathway, respectively. The overall survival of these two groups was analyzed using the Kaplan-Meier Estimate, and the statistical difference between these groups was calculated using the log-rank test afterwards. Results: The log-rank test p-value is 2.086e-3, which indicates a significant difference in the overall survival between the two groups. It shows that the group with alterations in the Ras-Raf-MEK-Erk/JNK signaling pathway had a longer overall survival than the group without those alterations. The details are as follows: Conclusions: Ras-Raf-MEK-Erk/JNK pathway mutations are significantly associated with longer OS for lung SQCC patients. Mutations in this pathway can be a potential indicator for SQCC patients, but the biological reasons behind this relationship remain to be explored.[Table: see text]

scholarly journals The Jun N-terminal kinases signaling pathway plays a “seesaw” role in ovarian carcinoma: a molecular aspect

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Yingyu Dou ◽  
Xiaoyan Jiang ◽  
Hui Xie ◽  
Junyu He ◽  
Songshu Xiao
Keyword(s):  
Ovarian Cancer ◽  
Signaling Pathway ◽  
Driving Forces ◽  
Mapk Signaling ◽  
Jnk Pathway ◽  
Jnk Signaling ◽  
Gynecological Malignancy ◽  
Mitogen Activated Protein ◽  
Jnk Inhibitors ◽  
Jnk Signaling Pathway

Abstract Ovarian cancer is the most common gynecological malignancy that causes cancer-related deaths in women today; this being the case, developing an understanding of ovarian cancer has become one of the major driving forces behind cancer research overall. Moreover, such research over the last 20 years has shown that the Jun N-terminal kinase (JNK) signaling pathway plays an important role in regulating cell death, survival, growth and proliferation in the mitogen-activated protein kinases (MAPK) signaling pathway, an important pathway in the formation of cancer. Furthermore, the JNK signaling pathway is often regulated by an abnormal activation in human tumors and is frequently reported in the literature for its effect on the progression of ovarian cancer. Although the FDA has approved some JNK inhibitors for melanoma, the agency has not approved JNK inhibitors for ovarian cancer. However, there are some experimental data on inhibitors and activators of the JNK signaling pathway in ovarian cancer, but related clinical trials need to be further improved. Although the Jun N-terminal kinase (JNK) signaling pathway is implicated in the formation of cancer in general, research has also indicated that it has a role in suppressing cancer as well. Here, we summarize this seemingly contradictory role of the JNK signaling pathway in ovarian cancer, that ‘seesaws’ between promoting and suppressing cancer, as well as summarizing the application of several JNK pathway inhibitors in cancer in general, and ovarian cancer in particular.

scholarly journals Dexmedetomidine Ameliorates Acute Stress-Induced Kidney Injury by Attenuating Oxidative Stress and Apoptosis through Inhibition of the ROS/JNK Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Yongping Chen ◽  
Xiujing Feng ◽  
Xueyuan Hu ◽  
Jichen Sha ◽  
Bei Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Acute Stress ◽  
Death Receptor ◽  
Kidney Injury ◽  
Jnk Pathway ◽  
Jnk Signaling ◽  
Jnk Signaling Pathway

Acute stress induces tissue damage through excessive oxidative stress. Dexmedetomidine (DEX) reportedly has an antioxidant effect. However, protective roles and related potential molecular mechanisms of DEX against kidney injury induced by acute stress are unknown. Herein, rats were forced to swim 15 min followed by restraint stress for 3 h with/without DEX (30 μg/kg). Successful model establishment was validated by an open-field test. Assessment of renal function (creatinine, urea nitrogen), histopathology, oxidative stress (malondialdehyde, glutathione, and superoxide dismutase), and apoptosis (transferase-mediated dUTP nick end labeling) was performed. Localization of apoptosis was determined by immunohistochemistry of cleaved caspase 3 protein. In addition, key proteins of the death receptor-mediated pathway, mitochondrial pathway, endoplasmic reticulum stress (ERS) pathway, and ROS/JNK signaling pathway were measured by Western blot. We found that DEX significantly improved renal dysfunction, ameliorated kidney injury, reduced oxidative stress, and alleviated apoptosis. DEX also inhibited the release of norepinephrine (NE), decreased the production of reactive oxygen species (ROS), and inhibited JNK phosphorylation. Additionally, DEX downregulated the expression of Bax, cytochrome C, cleaved caspase 9, and cleaved caspase 3 proteins in mitochondria-dependent pathways. In summary, DEX protects against acute stress-induced kidney injury in rats by reducing oxidative stress and apoptosis via inhibition of the ROS/JNK pathway.

scholarly journals Myc is involved in Genistein protecting against LPS-induced myocarditis in vitro through mediating MAPK/JNK signaling pathway

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Chunhua Huang ◽  
Yan Zhang ◽  
Hongli Qi ◽  
Xintan Xu ◽  
Lin Yang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Mapk Pathway ◽  
Enrichment Analysis ◽  
Cell Counting ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protective Effects ◽  
H9c2 Cells ◽  
Jnk Signaling ◽  
Jnk Signaling Pathway

Abstract Background: Genistein is widely used as a pharmacological compound as well as a food additive. However, the pharmaceutical effects of Genistein on myocarditis and its potential mechanisms have not been studied in detail. Methods: H9c2 cells were continuously stimulated by lipopolysaccharide (LPS) for 12 h to simulate the in vitro model of myocarditis injury. DrugBank, String, and GEO dataset were used to investigate specific genes that interacting with Genistein. KEGG and GO enrichment analysis were employed to explore Myc-related signaling pathways. Biological behaviors of H9c2 cells were observed with the support of cell counting kit-8, MTT and flow cytometry. Expression levels of cytokines including TNF-α and ILs were evaluated by enzyme-linked immunosorbent assay. Western blot was applied to detect the expression of Myc and MAPK pathway related proteins. Results: Genistein alleviated the damage of H9c2 cells subjected to LPS from the perspective of elevating cells growth ability, and inhibiting cells apoptosis and inflammatory response. Through bioinformatics analysis, we identified Myc as the potential target of Genistein in myocarditis, and MAPK as the signaling pathway. Significantly, Myc was highly up-regulated in myocarditis samples. More importantly, by performing biological experiments, we discovered that Genistein relieved H9c2 cells apoptosis and inflammatory reaction which caused by LPS stimulation through inhibiting Myc expression. Additionally, the marked augmentation of p-P38 MAPK and p-JNK expression in LPS-induced cardiomyocyte model were blocked by Genistein and si-Myc. Conclusions: Our research revealed that Myc mediated the protective effects of Genistein on H9c2 cells damage caused by LPS partly through modulation of MAPK/JNK signaling pathway.

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