Endocytosis of pro-inflammatory cytokine receptors and its relevance for signal transduction

2016 ◽  
Vol 397 (8) ◽  
pp. 695-708 ◽  
Author(s):  
Heike M. Hermanns ◽  
Julia Wohlfahrt ◽  
Christine Mais ◽  
Sabine Hergovits ◽  
Daniel Jahn ◽  
...  

Abstract The pro-inflammatory cytokines tumor necrosis factor (TNF), interleukin-1 (IL-1) and interleukin-6 (IL-6) are key players of the innate and adaptive immunity. Their activity needs to be tightly controlled to allow the initiation of an appropriate immune response as defense mechanism against pathogens or tissue injury. Excessive or sustained signaling of either of these cytokines leads to severe diseases, including rheumatoid arthritis, inflammatory bowel diseases (Crohn’s disease, ulcerative colitis), steatohepatitis, periodic fevers and even cancer. Studies carried out in the last 30 years have emphasized that an elaborate control system for each of these cytokines exists. Here, we summarize what is currently known about the involvement of receptor endocytosis in the regulation of these pro-inflammatory cytokines’ signaling cascades. Particularly in the last few years it was shown that this cellular process is far more than a mere feedback mechanism to clear cytokines from the circulation and to shut off their signal transduction.

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1516
Author(s):  
Ayodele Olaolu Oladejo ◽  
Yajuan Li ◽  
Xiaohu Wu ◽  
Bereket Habte Imam ◽  
Jie Yang ◽  
...  

In order to control and prevent bovine endometritis, there is a need to understand the molecular pathogenesis of the infectious disease. Bovine endometrium is usually invaded by a massive mobilization of microorganisms, especially bacteria, during postpartum dairy cows. Several reports have implicated the Gram-negative bacteria in the pathogenesis of bovine endometritis, with information dearth on the potentials of Gram-positive bacteria and their endotoxins. The invasive bacteria and their ligands pass through cellular receptors such as TLRs, NLRs, and biomolecular proteins of cells activate the specific receptors, which spontaneously stimulates cellular signaling pathways like MAPK, NF-kB and sequentially triggers upregulation of pro-inflammatory cytokines. The cascade of inflammatory induction involves a dual signaling pathway; the transcription factor NF-κB is released from its inhibitory molecule and can bind to various inflammatory genes promoter. The MAPK pathways are concomitantly activated, leading to specific phosphorylation of the NF-κB. The provision of detailed information on the molecular pathomechanism of bovine endometritis with the interaction between host endometrial cells and invasive bacteria in this review would widen the gap of exploring the potential of receptors and signal transduction pathways in nanotechnology-based drug delivery system. The nanotherapeutic discovery of endometrial cell receptors, signal transduction pathway, and cell biomolecules inhibitors could be developed for strategic inhibition of infectious signals at the various cell receptors and signal transduction levels, interfering on transcription factors activation and pro-inflammatory cytokines and genes expression, which may significantly protect endometrium against postpartum microbial invasion.


2013 ◽  
Vol 49 (12) ◽  
pp. 1190-1195 ◽  
Author(s):  
K. Krenke ◽  
J. Peradzyńska ◽  
J. Lange ◽  
A. Banaszkiewicz ◽  
I. Łazowska-Przeorek ◽  
...  

2004 ◽  
Vol 44 (5) ◽  
pp. 453 ◽  
Author(s):  
I. G. Colditz

The pro-inflammatory cytokines, IL-1, IL-6, TNFα and IFN α/β, produced during immune activation and tissue injury, override control of nutrient utilisation by the hypothalamic-somatotropic axis. The many effects of these cytokines include induction of fever and sickness behaviour, reduced fatty acid uptake by adipose tissue, reduced protein synthesis and enhanced protein breakdown in skeletal muscle, and gluconeogenesis, increased fatty acid synthesis and synthesis of acute phase proteins in the liver. Resistance to the effects of insulin, GH and IGF-1 is induced in adipose tissues, liver and muscle, at least in part through induction by pro-inflammatory cytokines of SOCS proteins which inhibit signal transduction and activation of gene transcription via the JAK/STAT pathway. These homeorhetic changes mobilise nutrients to fuel host defence responses. While an understanding of the mechanisms contributing to the catabolic state have arisen largely from studies of sepsis, trauma and acute challenge with biological mediators of the acute phase response, recent evidence in livestock suggests that graded production of pro-inflammatory cytokines during challenge with pathogens or subclinical infection can induce an incremental reduction in nutrient accretion in products of commercial value from livestock. This relationship highlights the value of good hygiene and reduced stress to improved feed utilisation for growth.


2020 ◽  
Vol 21 (18) ◽  
pp. 6963
Author(s):  
Jihun Shin ◽  
Hwa Young Song ◽  
Mina Lee

Limonoids, a dominant group of phytochemicals in the Rutaceae family, are known to exhibit several pharmacological activities. To identify natural products having efficacy against inflammatory bowel disease (IBD), we isolated 13 limonoids including a new compound, methyl sudachinoid A, from the seeds of Citrus junos and investigated their anti-inflammatory effects by assessing the expression of pro-inflammatory cytokines in lipopolysaccharide-stimulated RAW 264.7 mouse macrophages and HT-29 human colon epithelial cells. Our findings revealed that limonoids significantly downregulated the pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α, and nuclear transcription factor κB. In particular, sudachinoid-type compounds, methyl sudachinoid A and sudachinoid B, and ichangensin-type compound, 1-O-methyichangensin downregulated the expression of pro-inflammatory cytokines more potently than other limonoids, nomilin and limonin, which have been previously reported to exhibit anti-inflammatory activities in other cells; nomilin and limonin were therefore employed as positive controls in this study. Herein, we reveal that the anti-inflammatory activities of limonoids including a new compound methyl sudachinoid A from C. junos were mediated via the downregulation of pro-inflammatory cytokines and these limonoids can be employed as potential therapeutic phytochemicals for IBD.


2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Masooma Sultani ◽  
Andrea M. Stringer ◽  
Joanne M. Bowen ◽  
Rachel J. Gibson

“Mucositis” is the clinical term used to describe ulceration and damage of the mucous membranes of the entire gastrointestinal tract (GIT) following cytotoxic cancer chemotherapy and radiation therapy common symptoms include abdominal pain, bloating, diarrhoea, vomiting, and constipation resulting in both a significant clinical and financial burden. Chemotherapeutic drugs cause upregulation of stress response genes including NFκB, that in turn upregulate the production of proinflammatory cytokines such as interleukin-1β (IL-1β), Interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α). These proinflammatory cytokines are responsible for initiating inflammation in response to tissue injury. Anti-inflammatory cytokines and specific cytokine inhibitors are also released to limit the sustained or excessive inflammatory reactions. In the past decade, intensive research has determined the role of proinflammatory cytokines in development of mucositis. However, a large gap remains in the knowledge of the role of anti-inflammatory cytokines in the setting of chemotherapy-induced mucositis. This critical paper will highlight current literature available relating to what is known regarding the development of mucositis, including the molecular mechanisms involved in inducing inflammation particularly with respect to the role of proinflammatory cytokines, as well as provide a detailed discussion of why it is essential to consider extensive research in the role of anti-inflammatory cytokines in chemotherapy-induced mucositis so that effective targeted treatment strategies can be developed.


Sign in / Sign up

Export Citation Format

Share Document