Positive feedback loop of interleukin-1β upregulating production of inflammatory mediators in human intervertebral disc cells in vitro

2005 ◽  
Vol 2 (5) ◽  
pp. 589-595 ◽  
Author(s):  
Kotaro Jimbo ◽  
Jin Soo Park ◽  
Kimiaki Yokosuka ◽  
Kimiaki Sato ◽  
Kensei Nagata
Keyword(s):  
Intervertebral Disc ◽  
Positive Feedback ◽  
Protein Concentration ◽  
Feedback Loop ◽  
Serum Free Medium ◽  
Free Medium ◽  
Positive Feedback Loop ◽  
Content Type ◽  
Cox 2 ◽  
Fine Print

Object. Interleukin-1β (IL-1β) induces neurological symptoms in intervertebral disc herniation (IDH). Recently, the existence of a positive feedback loop of IL-1β, which encourages an inflammatory reaction or degeneration in the cells of tendon, has been reported. The authors hypothesized that there is a positive feedback loop of IL-1β in the cells of IDH. Methods. Eight human intervertebral disc specimens were harvested during spinal surgery for lumbar disc herniation. The cells were stimulated in serum-free medium with or without exogenous IL-1β. The messenger RNA (mRNA) was extracted for reverse-transcription polymerase chain reaction (PCR) and real-time PCR to quantify the mRNA of endogenous IL-1β, IL-6, cyclooxygenase-2 (COX-2), and matrix metalloproteinases (MMPs). The cells were then stimulated in serum-free medium with or without exogenous IL-1β, and then exogenous IL-1β was removed. After 2, 4, and 6 days, the medium was collected, and enzyme-linked immunosorbent assay was used to measure the protein concentration of endogenous IL-1β. The mRNA expressions of endogenous IL-1β, IL-6, COX-2, and MMPs were increased significantly depending on the concentration of exogenous IL-1β. The protein concentration of endogenous IL-1β was increased over time. Conclusions. There was a positive feedback loop of IL-1β in the cells of IDH. Furthermore, the productions of IL-6, COX-2, MMP-1, and MMP-3 were upregulated as a result of the increasing concentration of IL-1β in a positive feedback loop of IL-1β. The authors concluded that this positive feedback loop of IL-1β upregulated the production of mediators and thus can cause cessation of symptoms in IDH.

PGE2 potentiates tonicity-induced COX-2 expression in renal medullary cells in a positive feedback loop involving EP2-cAMP-PKA signaling

2009 ◽  
Vol 296 (1) ◽  
pp. C75-C87 ◽  
Author(s):  
Daniela Steinert ◽  
Christoph Küper ◽  
Helmut Bartels ◽  
Franz-X. Beck ◽  
Wolfgang Neuhofer
Keyword(s):  
Osmotic Stress ◽  
Cell Survival ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Mdck Cells ◽  
Dominant Negative ◽  
Dibutyryl Camp ◽  
Positive Feedback Loop ◽  
Cox 2 ◽  
Medullary Cells

Cyooxygenase-2 (COX-2)-derived PGE2 is critical for the integrity and function of renal medullary cells during antidiuresis. The present study extended our previous finding that tonicity-induced COX-2 expression is further stimulated by the major COX-2 product PGE2 and investigated the underlying signaling pathways and the functional relevance of this phenomenon. Hyperosmolality stimulated COX-2 expression and activity in Madin-Darby canine kidney (MDCK) cells, a response that was further increased by PGE2-cAMP signaling, suggesting the existence of a positive feedback loop. This effect was diminished by AH-6809, an EP2 antagonist, and by the PKA inhibitor H-89, but not by AH-23848, an EP4 antagonist. The effect of PGE2 was mimicked by forskolin and dibutyryl-cAMP, suggesting that the stimulatory effect of PGE2 on COX-2 is mediated by a cAMP-PKA-dependent mechanism. Accordingly, cAMP-responsive element (CRE)-driven reporter activity paralleled the effects of PGE2, AH-6809, AH-23848, H-89, forskolin, and dibutyryl-cAMP on COX-2 expression. In addition, the stimulatory effect of PGE2 on tonicity-induced COX-2 expression was blunted in cells transfected with dominant-negative CRE binding (CREB) protein, as was the case in a COX-2 promoter reporter construct in which a putative CRE was deleted. Furthermore, PGE2 resulted in PKA-dependent phosphorylation of the pro-apoptotic protein Bad at Ser155, a mechanism that is known to inactivate Bad, which coincided with reduced caspase-3 activity during osmotic stress. Conversely, pharmacological interruption of the PGE2-EP2-cAMP-PKA pathway abolished Ser155 phosphorylation of Bad and blunted the protective effect of PGE2 on cell survival during osmotic stress. These observations indicate the existence of a positive feedback loop of PGE2 on COX-2 expression during osmotic stress, an effect that apparently is mediated by EP2-cAMP-PKA signaling, and that contributes to cell survival under hypertonic conditions.

scholarly journals Interaction of Apoptotic Cells with Macrophages Upregulates COX-2/PGE2and HGF Expression via a Positive Feedback Loop

2014 ◽  
Vol 2014 ◽  
pp. 1-17 ◽  
Author(s):  
Ji Yeon Byun ◽  
Young-So Youn ◽  
Ye-Ji Lee ◽  
Youn-Hee Choi ◽  
So-Yeon Woo ◽  
...  
Keyword(s):  
Positive Feedback ◽  
Tissue Repair ◽  
Feedback Loop ◽  
Apoptotic Cell ◽  
Raw 264.7 Cells ◽  
Apoptotic Cells ◽  
Positive Feedback Loop ◽  
Cox 2

Recognition of apoptotic cells by macrophages is crucial for resolution of inflammation, immune tolerance, and tissue repair. Cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) and hepatocyte growth factor (HGF) play important roles in the tissue repair process. We investigated the characteristics of macrophage COX-2 and PGE2expression mediated by apoptotic cells and then determined how macrophages exposed to apoptotic cellsin vitroandin vivoorchestrate the interaction between COX-2/PGE2and HGF signaling pathways. Exposure of RAW 264.7 cells and primary peritoneal macrophages to apoptotic cells resulted in induction of COX-2 and PGE2. The COX-2 inhibitor NS-398 suppressed apoptotic cell-induced PGE2production. Both NS-398 and COX-2-siRNA, as well as the PGE2receptor EP2 antagonist, blocked HGF expression in response to apoptotic cells. In addition, the HGF receptor antagonist suppressed increases in COX-2 and PGE2induction. Thein vivorelevance of the interaction between the COX-2/PGE2and HGF pathways through a positive feedback loop was shown in cultured alveolar macrophages followingin vivoexposure of bleomycin-stimulated lungs to apoptotic cells. Our results demonstrate that upregulation of the COX-2/PGE2and HGF in macrophages following exposure to apoptotic cells represents a mechanism for mediating the anti-inflammatory and antifibrotic consequences of apoptotic cell recognition.

scholarly journals TLR4 signaling promotes a COX-2/PGE2/STAT3 positive feedback loop in hepatocellular carcinoma (HCC) cells

2015 ◽  
Vol 5 (2) ◽  
pp. e1074376 ◽  
Author(s):  
Ang Lin ◽  
Guan Wang ◽  
Huajun Zhao ◽  
Yuyi Zhang ◽  
Qiuju Han ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Positive Feedback Loop ◽  
Tlr4 Signaling ◽  
Cox 2 ◽  
Hcc Cells

scholarly journals Flagellar Stators Activate a Diguanylate Cyclase To Inhibit Flagellar Stators

2019 ◽  
Vol 201 (18) ◽  
Author(s):  
Daniel B. Kearns
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Secondary Metabolite ◽  
Positive Feedback ◽  
Biofilm Formation ◽  
Feedback Loop ◽  
Diguanylate Cyclase ◽  
Positive Feedback Loop ◽  
Content Type ◽  
Dependent Inhibition

ABSTRACT The bacterial secondary metabolite cyclic di-GMP is a widespread, cytoplasmic signal that promotes a physiological transition in which motility is inhibited and biofilm formation is activated. A paper published in this issue (A. E. Baker, S. S. Webster, A. Diepold, S. L. Kuchma, E. Bordeleau, et al., J Bacteriol 201:e00741-18, 2019, https://doi.org/10.1128/JB.00741-18) makes an important connection between cyclic di-GMP and flagellar components. They show that stator units, which normally interact with the flagellum to power rotation, can alternatively interact with and activate an enzyme that synthesizes cyclic di-GMP in Pseudomonas aeruginosa. Moreover, the same stator units are also the target of cyclic-di-GMP-dependent inhibition such that the more the stators are inhibited, the more cyclic di-GMP is made. The resulting positive-feedback loop not only inhibits motility but also may initiate and stabilize biofilm formation.

scholarly journals A Positive Feedback Loop that Regulates Cyclooxygenase-2 Expression and Prostaglandin F2α Synthesis via the F-Series-Prostanoid Receptor and Extracellular Signal-Regulated Kinase 1/2 Signaling Pathway

Endocrinology ◽  
2005 ◽  
Vol 146 (11) ◽  
pp. 4657-4664 ◽  
Author(s):  
Henry N. Jabbour ◽  
Kurt J. Sales ◽  
Sheila C. Boddy ◽  
Richard A. Anderson ◽  
Alistair R. W. Williams
Keyword(s):  
Positive Feedback ◽  
Feedback Loop ◽  
Endometrial Adenocarcinoma ◽  
Prostaglandin F2α ◽  
Receptor Activation ◽  
Receptor Interaction ◽  
Dominant Negative Mutant ◽  
Positive Feedback Loop ◽  
Fp Receptor ◽  
Cox 2

Cyclooxygenase (COX) enzymes catalyze the biosynthesis of eicosanoids, including prostaglandin (PG) F2α. PGF2α exerts its autocrine/paracrine function by coupling to its G protein-coupled receptor [F-series-prostanoid (FP) receptor] to initiate cell signaling and target gene transcription. In the present study, we found elevated expression of COX-2 and FP receptor colocalized together within the neoplastic epithelial cells of endometrial adenocarcinomas. We investigated a role for PGF2α-FP receptor interaction in modulating COX-2 expression and PGF2α biosynthesis using an endometrial adenocarcinoma cell line stably transfected with the FP receptor cDNA (FPS cells). PGF2α-FP receptor activation rapidly induced COX-2 promoter, mRNA, and protein expression in FPS cells. These effects of PGF2α on the expression of COX-2 could be abolished by treatment of FPS cells with an FP receptor antagonist (AL8810) and chemical inhibitor of ERK1/2 kinase (PD98059), or by inactivation of ERK1/2 signaling with dominant-negative mutant isoforms of Ras or ERK1/2 kinase. We further confirmed that elevated COX-2 protein in FPS cells could biosynthesize PGF2αde novo to promote a positive feedback loop to facilitate endometrial tumorigenesis. Finally, we have shown that PGF2α could potentiate tumorigenesis in endometrial adenocarcinoma explants by inducing the expression of COX-2 mRNA.

scholarly journals The strengths and capacities of Authentic Followership

2016 ◽  
Vol 37 (3) ◽  
pp. 310-324 ◽  
Author(s):  
Deanna de Zilwa
Keyword(s):  
Positive Feedback ◽  
Feedback Loop ◽  
Organisational Culture ◽  
Positive Outcomes ◽  
Dyadic Relationships ◽  
Organisational Performance ◽  
Positive Feedback Loop ◽  
Content Type ◽  
Authentic Followership ◽  
Three Components

Purpose – Exploring a new conceptual framework for authentic followership (AF) comprised of three components: individual, dyadic and organisational. The purpose of this paper is to explain how the components of AF interact as a positive, non-linear feedback loop. It presents three propositions of positive outcomes arising from AF. First, AF builds follower’s strengths and capacities. Second, AF strengthens dyadic relationships between followers and leaders. Third, AF deepens and strengthens positive organisational culture thereby improving organisational performance. It discusses the practical significance of these propositions for followers, leaders and firms. Design/methodology/approach – The paper provides an overview of AF. Then three propositions of positive outcomes arising from AF are presented. It identifies how these propositions could benefit followers, leaders and firms. In conclusion, it offers suggestions for future research directions and notes some limitations of this work. Findings – The key finding of this paper is that AF could potentially strengthen the capacities and performance of followers, leaders and organisations if the propositions presented in this work are correct – if the three components of AF interact with each other as a positive feedback loop strengthening and reinforcing each component of AF. To establish the validity of the AF model and the three propositions the paper suggests that investigations in different empirical settings are undertaken: SME’s and multinational corporations, in different countries under different market conditions, with followers and leaders of different gender, age, education level, roles and tenure of employment. Originality/value – The paper’s core contention that the components of AF interact as a positive feedback loop has significant practical implications – beneficial outcomes for followers, leaders and firms. P1 explains how AF enables followers to gain confidence, maturity and create solid foundations from which to thrive and flourish. P2 explains how dyadic relationships between followers and leaders could be strengthened, deepening trust and respect between each party, thereby enhancing leadership effectiveness. P3 explains how the dynamic processes of AF can strengthen and deepen positive organisational culture and enhance organisational performance.

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