Role of SOCS3 in Disease Pathology - Literature Review Example

For the cells in a body to work effectively to perform a given activity as a unit, effective communication between them is necessary. Within the body, the communication between cells is facilitated by the growth factor network and cytokines within the body. The suppressors of cytokine signaling (SOCS) proteins control the production and evoke reactions from transduction signal responses from other cytokines and growth factors. In consequence, the gene controls and regulates cytokine signal transduction. There is need to control the release of cytokines and responses to them since they in turn influence infections, proper development of immune cell populations, and prevention of infections that are associated with immunopathology.

Since the cytokines coordinate various immune responses in the body, the Janus Kinase (JAK) a common and stable form of protein formed by the association between cytokine receptors and cytoplasmic tyrosine kinase is activated. The activity of the JAK is activated as a result of the binding of two receptor molecules, and as a result of dimerization, the two JAKs are brought close such that they can phosphorylate each other. The signal transducer and activator of transcription (STAT) proteins that facilitate the signaling pathway attach on the residue of the phosphotyrosine. Once brought into proximity to a JAK that phosphorylates, the STAT can start binding with the specific DNA sequences. As a result, there is an evident signaling pathway where information from the DNA is communicated constantly. Each cytokine will bind to a specific receptor and respond to a certain set of genes. Thus, its reactions within a cell will always be specific for that matter. SOCS3 plays a significant role in regulating cytokines and the cytokine receptors, and in the process, it influences the health of an individual. It tends to regulate by suppressing the binding to JAK and cytokine receptors. To be specific, it appears to have generated a ternary complex where the two molecules, despite their higher overall affinity to go over and above individual association. Such inhibition may result into several associated diseases since the immune system is weakened with any reduction in the SOCS proteins. Some of the conditions associated with SOCS3 upregulation include Multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis, cardiovascular diseases, cancer, obesity and insulin resistance, etc. In consequence, this literature will review the relationship between the SOCS3 and associated diseases and from the studies derive the appropriate therapeutic implication for doctors to consider.

SOCS3 and Associated Diseases

SOCS3 and Multiple Sclerosis

Multiple sclerosis is an autoimmune disease where the bodys immune system plays a pathogenic role in its formation especially if there is abnormal activation of JAK/STAT pathway. Aberrant levels of cytokines/chemokines are expressed in the CNS after macrophages and microglia are activated where the abnormal high levels could cause demyelination and neuronal damage. The animal model for multiple sclerosis is the experimental autoimmune encephalomyelitis (EAE) that has T-cells within which CD4 Th1 and Th17 cells are produced. However, in the system, the Th2 and Treg cells can resolve the disease. Within the CNS, the macrophages and microglia can cause both injury and repair depending on the cellular microenvironment that induces their polarization.

STAT3 is the gene susceptible to multiple sclerosis. Most of the patients diagnosed with the disease tend to express an unusually increased activation level of STAT3 and less expression of the SOCS3 suppression molecules. This suggests that there is an apparent association between the reduced expression of SOCS3 and increased activation of STAT3 and relapse from multiple sclerosis. By assuming that SOCS3 expression will protect cells against neuroinflammation and neurodegeneration, a STAT3/SOCS3 relationship in myeloid cells could influence the polarization of M1, neuronal viability in UAE/multiple sclerosis and T-cell repertoire. Therefore, an understanding of the STAT3/SOCS3 axis in neuroinflammation could lead to the conception of rational therapeutic option for patients.

SOCS3 and Inflammatory Bowel

The Inflammatory bowel disease (IBD) could be either Ulcerative Colitis (UC) or the Crohns disease (CD). Though the disease is chronic, its pathogenesis is still unknown to the people; however, scientists believe that it results from a dysregulated, aberrant immune response to intestinal flora in a context of genetic predisposition. Cytokines disrupt the normal state of controlled inflammation yet they are key signals within the intestinal immune system. Lymphocytes and APCs are responsible for the IBD mainly due to the present production of TNF-a, a 17-kD pleiotropic cytokine. These, in turn, are produced by the innate immune cells, for example, monocytes, macrophages, and differentiated T-cells. TNF-a induces inflammatory effects by producing IL-1b and IL-6. In fact, the TNF-a were evident in most of the patients suffering from CD and UC, which indicates high disease activity in their bodies.

Through STAT signaling, the cytokines may be transmitted to different cells, which could promote the disease within the body that has disastrous effects on the individual in question. Consequently, the only way to control the inflammation and ensure that the cytokines may not cause health hazards to the human body, the SOCS3 plays a huge role. In fact, the heightened expression of the SOCS3 proteins results in the pathology under such increased production of cytokines in the body. Beneath the gut epithelia, an M2 phenotype is maintained by the lamina propria macrophages phagocytose bacteria. Most of the patients of the inflammatory disease (that is both UC and CD) have over 40 percent expression of SOCS that leads to the activation of the M1- activate macrophages among other things that lead to IBD associated inflammation especially peroxisome proliferator-activated receptor. In its treatment, an up-regulation of SOCS3 associated with macrophages lacking peroxisome proliferator-activated receptor was used.

SOCS3 and Rheumatoid Arthritis

Rheumatoid Arthritis (RA) is a chronic disease without a discovered etiology that affects synovial joints that are as a result of the impossibility to regulate either adaptive or innate immunity. This is as a result of the altered functioning of cells due to the defective regulation of individual signal transduction pathways of the JAK/STAT. Other than the deregulated transductions of signals in the RA joint tissues continuous activation between the signaling pathways is likely to make the situation worse. Though MAs main cause is still unknown to human beings, the cytokines have been suggested as one of its causes since it has pro-inflammatory factors including TNF- a, IL-1 and IL-6. Science has indicated that a number of cancers are similarly activated by the continuously activated JAK/STAT signaling. Similarly, the continued activation of the JAK/STAT is continuously associated with SOCSs up-regulation. Despite SOCS3s ability to give rise to positive effects in human beings, it is evident that they were also as much harmful to people especially when they are not regulated well. Since the SOCS3 was determined to play a negative role in its inhibition of JAK and cytokine signal transduction, it has a negative regulatory effect on IL-6 signaling pathway. In consequence, it is likely to result in diseases correspondingly as in the previous sections. The up-regulation of the protein is the most indisputable cause of the disease produced so far.

SOCS proteins and Obesity

Similar as in the case of RU, the SOCS3 proteins restrains responses macrophages of the IL-6 and Leptin, which end up getting up-regulated as well as to result in the problem. Insulin signaling is also inhibited by SOCS3, which makes an individual to be sensitive to insulin despite being in the state of obesity. Obesity is as a result involves the defects in the resistance of insulin and metabolism of energy that is associated with low-grade inflammation. For that matter, the SOCS3 in obese individuals is produced in their skeletal muscles. Research confirms that the SOCS3 within the body tends to inhibit the signaling of leptin and insulin transduction, which may be the actual cause of obesity. Despite being produced in the skeletal muscles of the body, it is not of any help to the development of the respective muscles in the body or during the process of energy expenditure, yet despite this, it inhibits the body from being insulin sensitive. To be precise, the SOCS family of proteins (both SOCS1 and SOCS3) that bind to the tyrosine phosphorylation through their SH2 domain will end up inhibiting inflammatory signal transduction. In addition, to the hypothalamus, adipose tissues and liver, the SOCS3 will also increase with obesity. In addition, SOCS3 is a negative regulator of insulin signaling; hence its deletion could enhance its signaling. Unlike the skeletal muscles, however, obesity resulting from insulin resistance cannot be treated by inhibiting SOCS3.

SOCS3 and Cancer

The two macrophages, M1 and M2 usually play a different role in the identification and dealing with cancerous cells. For example, SOCS3 identifies macrophages that have enhanced the ability to kill the tumors whereas the SOCS1 produces M2, which tend to favor the survival of the tumor in the body. As a result, increasing the SOCS3 in the body and reducing the SOCS1 may go a long way in the maintenance of peoples health especially against dangerous tumors in the body since there is increased response to tumors in the body. On the other hand, macrophage deletion of SOCS3 in the Mice being experimented with by Edward, Ralph and Bradshow showed increased metastasis in the cells that that could explain peoples susceptibility to cancer since IL-6 and TNT- a production in the cells is affected.

Therapeutic implications

Given that the activities of the SOCS proteins in the body, especially as they affect the macrophages in the body, they ought to be treated with care. However, the various implications of regulating SOCS (SOCS3 and SOCS1) gives rise to various therapeutic opportunities of the immune and inflammatory responses within the body. Depending on the expected reaction of the process of regulation, science should be able to take advantage of these opportunities to improve the health of the individuals by ensuring the effective transduction of signals and regulation of the cytokines in the body. This suggests that therapists ought to always consider the positive advantages associated with SOCS3 regulation in its signaling effect on STAT3 to protect the body against the various diseases that are associated with SOCS3 regulation. For instance, in the case of obesity, the regulation of SOCS3 is important since it would lead to the better regulation of leptin and insulin transduction process, which could prove important for individuals.

Conclusion

From the discussion above, it is clear that the regulation of cytokines in the body. The cytokines are best regulated by the SOCS class of proteins. The binding of the JAK and the STA in the body is the first in enhancing the immune processes of the body. The SOCS proteins regulate the immune responses by inhibiting the cytokine receptors from binding with the JAK. As a result of the process of binding inhibition, the SOCS (especially SOCS3) plays an important, indispensable role in the body. That is, the ability to inhibit the JAK from binding to the receptors it protects the body against various chronic diseases, which may even lead to the death of the sick person. This implies that the SOCS3 has an irrefutable effect on the causation o...