What role does NF-Kappa B have in pregnancy and parturition?
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What Role Does NF-kappaB Have in Pregnancy and Parturition?
NF-KappaB is a protein that is involved in the transcription of DNA, cytokine production and cell survival. NF-KappaB is involved in lots of biological processes such as inflammation, immunity, differentiation, cell growth and apoptosis. The protein is found to be involved in cellular responses to stimuli e.g. stress, cytokines, free radicals, heavy metals, UV and antigens (bacterial, viral).
NF-KappaB is a protein complex where generally two different proteins combine together (Heterodimer). It is a universal transcription factor. NF-KappaB is present in all cells of our body. Whenever our body is in distress or in any kind of stress from an outside stimulus, the first signalling pathway that will be activated is the NF-KappaB signalling. This is important because it would respond to and prepare our body against any environmental changes that our body is facing. NF-KappaB is the first responder to harmful cellular stimuli. NF-KappaB starts the process of cellular healing and all other physical cellular pathways that leads to fixing any errors and damage that have occurred. There are five important parameters in the signalling pathway; 1. Signalling molecule in NF-KappaB e.g. R.OS, Ionizing radiation, IL-1, TNF alpha/beta, and different foreign origins. 2.Receptors involved in NF-KappaB signalling e.g. TLR, TNFR, Receptor Activator of NF-KappaB, and ROS. 3. Cellular Activators or second messengers e.g. IKK (IKB Kinase), IKB (inhibitor of NF-KappaB), and NFKB. 4.Transcription factors e.g. NF-KappaB. 5. Cellular effects of the NF-KappaB pathway e.g. DNA transcription, cytokine production, and cell survival. The NF-KappaB signalling pathway is understood by when a signal from the outside binds to the receptor on the cell membrane and activates the receptor. After activation of the receptor the IKK will phosphorylate the IkBalpha. Proteasome degradation will occur, releasing the IkBalpha from the NF-KappaB (ReIA+P50). ReIA+P50 (NF-KappaB) will be activated after the release of IkBalpha, entering into the nucleus of the cell. It will combine with other coactivators and RNA Polymerase, where it will go to the nuclear DNA. Transcription of the gene will occur and the mRNA will be transported to the cytosol. Ribosomes will translate the protein where it will be used for cellular action e.g. DNA transcription, Cytokine production, and Cell survival.
NF-KappaB is a universal transcription factor which generally is formed by two different proteins combining together (Heterodimer). During stress from an external stimulus, the body will initiate the NF-KappaB signalling as the first signalling pathway to deal with those effects. This is vital due to the signalling pathway prepares the body against any negative impact that may occur from such events. NF-KappaB is the first responder to harmful cellular stimuli. NF-KappaB starts the process of cellular healing and all other physical cellular pathways that leads to fixing any errors and damage that have occurred. There are five important parameters in the signalling pathway; 1. Signalling molecule in NF-KappaB e.g. R.OS, Ionizing radiation, IL-1, TNF alpha/beta, and different foreign origins. 2.Receptors involved in NF-KappaB signalling e.g. TLR, TNFR, Receptor Activator of NF-KappaB, and ROS. 3. Cellular Activators or second messengers e.g. IKK (IKB Kinase), IKB (inhibitor of NF-KappaB), and NFKB. 4.Transcription factors e.g. NF-KappaB. 5. Cellular effects of the NF-KappaB pathway e.g. DNA transcription, cytokine production, and cell survival. The NF-KappaB signalling pathway is understood by when a signal from the outside binds to the receptor on the cell membrane and activates the receptor. After activation of the receptor the IKK will phosphorylate the IkBalpha. Proteasome degradation will occur, releasing the IkBalpha from the NF-KappaB (ReIA+P50). ReIA+P50 (NF-KappaB) will be activated after the release of IkBalpha, entering into the nucleus of the cell. It will combine with other coactivators and RNA Polymerase, where it will go to the nuclear DNA. Transcription of the gene will occur and the mRNA will be transported to the cytosol. Ribosomes will translate the protein where it will be used for cellular action e.g. DNA transcription, Cytokine production, and Cell survival.
What Role Does NF-kappaB Have in Pregnancy and Parturition?
Introduction
NF-KappaB is a universal transcription factor that plays a role in regenerating the immune responses to any stress stimuli and is associated with inflammation. Due to stress from an external stimulus, the body will initiate the NF-KappaB signalling as the first signalling pathway to deal with those effects. The significance of NF-KappaB is its fast response to harmful cellular stimuli. NF-KappaB starts the process of cellular healing and all other physical cellular pathways that leads to fixing any errors and damage that have occurred. This signalling pathway is understood by when an external stimulus, e.g. TNFalpha, IL-1beta and LPS, binds to the receptor on the cell membrane and activates the receptor. In doing so, the kinase complex activates and two phosphate groups attach to the IKKbeta leading to its phosphorylation. Throughout the process of the attachment of two phosphate groups Ubiquitin recognizes it and attaches itself to the IKKbeta. The phosphate groups loosely bound the complex to the Ubiquitin and undergoes Ubiquitination in which the ubiquitin detaches from the complex. Additionally, leading P50+ReIA (NF-KappaB) to enter the nucleus to undertake translation for the release of COX-2.
Pregnancy and Parturition
NF-KappaB activity increases during the onset of labor and is suppressed during the first trimester of pregnancy (King et al. 2001). In the state of parturition, the NF-KappaB would be at its highest peak since the membrane ruptures, fetal maturation, placental separation that takes place. These would indicate that an increased influx of inflammatory cells would be present, allowing haram to the fetus (preterm labor to occur). In the study it has been said that during pregnancy the NF-KappaB would be suppressed to prevent any preterm labor to occur. (King et al. 2001) stated that the during the first trimester when NF-KappaB activation is suppressed, the mucous membrane that lines in the uterus during pregnancy and is shed afterbirth called the decidua is contributed to the immunosuppressive mechanisms that occur during pregnancy. While studying human labor it has shown no direct link between the onset of labor and NF-KappaB through no genomic or genetic reports. In this study it is stated that the activation of the NF-KappaB as a result of changes in the mechanism which regulates the NF-KappaB could be occurring in labor or the premature activation of NF-KappaB could result in preterm labor. The research in humans has focused on 3 specific things. 1. Is to determine if the activity of NF-KappaB proteins are increased in the uterus with labor. 2. Examine the triggers of labor to check the activation of NF-KappaB. 3. Checking what is needed in the pro-labor pathways for NF-KappaB mediated transcription. In the study (Allport et al. (2001)) said that increased transcriptional activity of NF-Kappa is seen in the amnion cells in spontaneous labor relative to the levels in the amnion cells at term. This has suggested that NF-KappaB plays an important role in the amnion at labor. (Mohan et al. 2005) said that in the amnion cells, when the myometrium stretches during pregnancy it activates the NF-KappaB. The activation of the NF-KappaB will induce the COX-2. COX-2 is an enzyme that is needed for prostaglandin productions. It has been said that NF-KappaB plays an important role labor associated inflammation. NF-KappaB is activated by a stimulus which induces labor, where it will regulate the expression of molecules that are in the process of parturition. A decline in sensitivity to progesterone has been important in the onset of labor, and NF-kB may counteract the PR to bring about a ‘functional’ progesterone withdrawal.
Conclusion
NF-KappaB is important as it takes part in multiple pathways that are involved in the onset of labor and contributes to the therapeutic aspect in the management of preterm labor. Studies have shown that treatments that were directed against the NF-Kappa had more effect then the current treatments and had an advantage that prevented harmful effects to the fetus that could have resulted from an infection or inflammation. It is understood that the current treatments were less advantageous then the treatment stated in this study which focuses primarily on treatments against the NF-KappaB. It has been shown that the treatment against the NF-KappaB has barred the harmful effects on the fetus from any external stimulus such as inflammation and infection. Due to the physiological role, the identification of labor specific NF-KappaB signaling components and the selective targeting of the NF-KappaB pathway is vital in lessening the toxicity of any potential new treatments for preterm labor. The efficiency of this approach depends most primarily on how early the process of NF-KappaB is activated in parturition and also in the development of enhanced diagnostic indicators in preterm labor for the intervention to be attained before any branching cascade has been taken place (Cornette, 2004).
