10 Responses

  1. Sidnee F.
    Sidnee F. at | | Reply

    I found this article to be interesting because it highlights the JNK pathway. After further research I was able to understand more about what this pathway is really doing inside the body. The JNK pathway helps in the proliferation, differentiation, cell death or survival and protein expression. It’s also linked to autoimmune diseases, cancers, and diabetes which are all examples of diseases that keep the body in an inflamed state. When the PPR NLR-P12 isn’t functioning properly, the innate immune cells are forced to act without the help of this PPR and thus starts the JNK pathway which also starts the inflammation process. NLR-P12 normally works to combat the inflammation process and carcinoma growth. The body transmits signals to release interleukins and these are present in the initial phases of liver diseases like HCV, a constant liver inflammatory disease. I do agree that if we could target NLR-P12, we could halt the inflammation process and be able to better target and cure diseases like HCV. The body’s overall health seems to go downhill when it’s in a constant state of inflammation. If this PPR is increased I think the activation of the JNK pathway would be reduced. This would limit the chances of the body targeting resident commensal bacteria and host cells so no inflammation could occur.


    1. Mengzhu Tang
      Mengzhu Tang at | | Reply

      From reading the post, I was most intrigued about the effects of the sensor Nlrp12 against hepatocellular carcinoma. And I totally agree with what you mentioned that if we could target Nlrp12, we could halt the inflammation process and be able to better target and cure diseases like HCV. By further reading, this research article below underscores a novel cancer suppressive pathway in the liver involving Nlrp12. They investigated the role of Nlrp12 in HCC using mouse models. The expression of Nlrp12 was seen negatively correlated with human HCC. Nlrp12-/- mice developed significantly higher tumor burden in the liver following administration of mutagens. HCC susceptibility in Nlrp12-/- mice was eliminated with antibiotics treatment. Our in vivo and in vitro data demonstrate that Nlrp12 negatively regulates HCC pathogenesis via downregulation of JNK-dependent inflammation and proliferation of hepatocytes. These results suggest the loss of Nlrp12 is associated with increased HCC susceptibility, so if the Nlrp12 is increased, the activation of the JNK pathway would be reduced, and the cancer-promoting signals and proliferation of hepatocytes would be inhibited.


  2. Kenton G
    Kenton G at | | Reply

    The concept of NOD-like receptors playing a role in combating tumor growth was new to me, so I wanted to do some more research on the subject. I found a great paper that brings together several topics that we have discussed in class and thought it was worth sharing. The research shows when a tumor cell dies it releases ATP, causing a cascade that leads to the targeting of cancerous cells. The ATP stimulates receptors on dendritic cells which causes the activation of the NLRP3 inflammasome within the dendritic cells. NLRP3 is important because the inflammasome triggers the release of the cytokine IL-2ß, which in turn allows for the dendritic cell to prime CD8+ T cells so that they are specific against the tumor antigens.

    We learned in class that the dendritic cells are the bridge between the innate immune response and the adaptive. I thought it was interesting to see that they can also act as the bridge to target tumor cells, thanks to NLRP3. In the original post, it was mentioned how chronic inflammation could lead to liver cancer. IL-2ß which is associated with chronic inflammation, was in this case, part of the reason CD8+ T cells were able to target the tumor cells. It would be interesting to see how many other cytokines have this dual role, and the feasibility of using them as an effective cancer treatment.


  3. Zachary Davis
    Zachary Davis at | | Reply

    This article intrigued me regarding the ability of immune cells to inhibit inflammation to control cancer progression. Particularly interesting is the process by which pathogenic bacteria possessing a lipopolysaccharide can induce inflammatory responses and provoke the development of cancers of the body. Fusobacterium nucleatum, for instance, utilizes its LPS layer to suppress immune function and enhance inflammation. Its LPS layer is particularly dangerous regarding the innate immune cells; it promotes M2 polarization of macrophages, resulting in them losing phagocytic capabilities and producing toxic chemicals that suppress or ward away other immune cells. This results in infiltration of the colorectal wall and the progression of cancer. It can be assumed that many of these cases are due to malfunctioning or absent NLRP12 genes, which, if correctly transcribed and expressed, can easily subdue infections and halt the progression of disease.


    OMOLOLA TAIWO at | | Reply

    I observed this article to intrigue since it features the JNK pathway. After further research, I had the capacity to see progressively what this pathway is truly doing inside the body. The JNK pathway helps in the expansion, separation, cell passing or survival, and protein articulation. It’s additionally connected to immune system infections, malignancies, and diabetes which are altogether instances of maladies that keep the body in an aggravated state. At the point when the PPR NLR-P12 isn’t working appropriately, the intrinsic resistant cells are compelled to act without the assistance of this PPR and therefore begin the JNK pathway which likewise begins the aggravation procedure. NLR-P12 regularly attempts to battle the irritation procedure and carcinoma development. The body transmits signs to discharge interleukins and these are available in the underlying periods of liver sicknesses like HCV, a consistent liver fiery ailment. I do concur that on the off chance that we could target NLR-P12, we could stop the irritation procedure and have the capacity to all the more likely target and fix ailments like HCV. The body’s general wellbeing appears to go downhill when it’s in a consistent condition of irritation. In the event that this PPR is expanded I figure the enactment of the JNK pathway would be diminished. This would confine the odds of the body focusing on inhabitant commensally microorganisms and host cells so no aggravation could happen.


  5. Donzell Jones
    Donzell Jones at | | Reply

    After reading this blog post, I found that immune cells possess many different mechanisms to reduce disease in the body including the use of sensors to regulate and suppress inflammation. By downregulating the JNK pathway signal, produced by tumor cells in the liver, NLRP12 is able to act as a therapeutic target to remove inflammation and inhibit cancer-promoting signals in damaged tissues. Since the depletion of NLRP12 results in the increase of tumor growth and high levels of inflammation, I concluded that using this immune cell receptor to treat cancer development is based primarily on its ability to stop JNK signaling. This is shown in a recent article where the authors test the involvement of the JNK pathway in the circumstance of different diseases and how we could harvest its components as therapeutic targets. By choosing this article, the authors also explained how apoptosis results in many cell deaths by the major role of JNK signaling. Thus, further proving my idea of NLRP12 function as a negative regulator of the inflammatory response. We are then able to test this theory of NLRP12 in the involvement of other cancers similar to liver cancer.


    1. Yiqi Tian
      Yiqi Tian at | | Reply

      I very much agree and appreciate your thoughts, stopping JNK signaling do great help on using the immune cell receptor to treat cancer. In the post, the author pointed out that antibiotics can be used to reduce levels of gut bacteria to prevent the JNK pathway is usually activated. What’s more, in your comment, you made use NLRP12 as a negative regulator in the inflammatory response. So I am thinking that in addition to reducing the activation and negative regulation of the JNK pathway, is there any JAK inhibitor? So I started further research and found an article, The Immunomodulatory and Anti-Inflammatory Role of Polyphenols. I think this article is very useful because it introduces JNK inhibitors, polyphenols to stopping JNK signaling. This article points out how polyphenols are as JNK inhibitor and used to respond to inflammatory. Polyphenols can interfere proinflammatory cytokines’ synthesis. They take advantage of mTORC1 which is a protein complex that controls protein synthesis, and JAK/STAT. They can also suppress toll- Like receptor and pro-inflammatory genes’ expression. My point of view is confirmed in the article, polyphenols are a good JNK inhibitor.

  6. Patrick Lindstrom
    Patrick Lindstrom at | | Reply

    I would like to agree with this post’s opinion of NLRP12 since the NLRP12 receptor was shown to be helpful in the protection against liver cancer cases. If this sensor were to be increased via a drug, the innate response to cases of liver cancer can be treated in a more efficient manner. In the article, a molecule called polyinosinic-polycytidylic acid systemically activated the innate immune system in a mouse with liver cancer. The mouse’s immune system displayed an improved response to the carcinoma and the carcinoma stopped growing. A drug that can ellicit this response may prove to be a useful anti-liver cancer medication.


  7. Susmita Dey
    Susmita Dey at | | Reply

    After reading this blog post, I was amazed to know that the human innate immune system contains a major sensor called NLRP12 which can suppress cancerous hepatocytes. The author mentioned that JNK in the liver cells get stimulated by gut bacterial LPS and due to its cause of inflammation, the NLRP12 in tissue cells downregulate the phosphorylation of JNK and inhibits cancer cell signals which leads the hepatocytes to proliferate. Thus, it is confirmed that NLRP12 has a major role to act as a therapeutic agent on treating liver cancer whereas JNK allows specific mutation to cause cell death. But, I am wondering if JNK has a potent function in the nervous system by upregulating kinases which allows brain development, repair, and memory formation. So I found a recent article, telling if the cell dies in liver which occurs due to JNK then inflammatory signals will be sent to the CNS as the body going through a functional change and the effect of it may cause neuroinflammation which might trigger the brain cells by local signal transmitter and may cause neuronal death or seizure. Therefore, it is important to know specific activities of JNK in the brain and nervous system before inducing NLRP12 in therapeutic method to cure liver cancer.


  8. AS
    AS at | | Reply

    I found the post to be interesting because of the finding of a novel function for NLRP12, uncovered by this study. Knowing that NLRP12 exists within the cytosol of innate immune cells seemed to indicate that the other immune functions of this pattern recognition receptor would be related to innate immune responses. However, I found this study by Gharagazloo et al., which investigated the role with T-cell mediated immune responses, using experimental autoimmune encephalomyelitis (EAE) in mice as a model for multiple sclerosis in humans. The results of this study build upon the results from a previous study by Lukens et al. in 2015, which discovered a regulatory role of NLRP12 in T-cell activation, by suppressing IL-4 production. In the more recent study, Gharagazloo et al. found that NLRP12 has a protective role in induced EAE by reducing the IFNγ/IL-4 ratio, suppresses IL-2 and IFNγ production, thereby suppressing Th1 responses, and inhibits T cell proliferation. Other parts of the paper discussed the inhibitory role of NLRP12 in the MAPK signaling pathway and Akt signaling pathway and subsequently the NF-κB signaling pathway.

    In addition to the broad range of regulatory activity that NLRP12 shows in regards to T cell activation and proliferation, the other interesting information included in this paper is the immunoregulatory role of NLRP12. Depending on the immunological challenge, ranging from low, medium, to high, the regulatory activity of NLRP12 can vary from inflammatory, bifunctional inflammatory and anti-inflammatory and inflammatory, respectively. Accordingly, it makes one think about the complexity of the immune system, how one seemingly simple receptor which plays a role in both innate and adaptive immunity, can have such varied and distinct effects.


Leave a Reply