Asthma’s heterogeneity has long been recognised. Your current understanding of asthma would lead you to realise that it is a multifaceted illness with few symptoms but many possible causes, including hereditary and environmental factors. Also, the widespread incidence of asthma among the general population has prompted the scientific community to search for potential treatments for the condition. Nevertheless, without understanding the underlying causes of asthma, this is not possible. Researchers from many countries have been looking into asthma treatment options. Amarjit Mishra of Auburn University has been playing a crucial role in helping to develop a better understanding of asthma and its many manifestations. Let’s learn more about Amarjit Mishra and how his work is influencing other researchers’ understanding of the causes and potential therapeutic targets of asthma heterogeneity.
At Auburn University, Amarjit Mishra is currently employed as an assistant professor. He is an accomplished researcher in the fields of immunology and pulmonology. In addition to being a well-known academician, Amarjit Mishra has participated in numerous projects approved by the National Institute of Health of the USA and made a name for himself in the field of biological sciences. For the past few years, the pathophysiology of asthma has been the focus of his significant research. He is working hard to identify prospective targets for treating asthma brought on by diverse circumstances, including asthma brought on by allergies.
Amarjit Mishra has made a groundbreaking discovery in one of his key publications, highlighting that the selective targeting of metabolic reprogramming can function as a potential therapy option for asthma. In order to further clarify the situation, Amarjit Mishra has drawn attention to previous studies that showed metabolic regulators involved in multiple catabolic and anabolic pathways could be one of the most promising therapeutic options for the treatment of asthma endotypes. Before his work, attempts have also been made earlier to focus on several therapeutic approaches to restore equilibrium when energy metabolism in asthmatic lungs changes, primarily studying the regulation of the leukotriene synthesis pathway or the use of L-arginine as a substrate. However, in one of his pioneer works Amarjit Mishra has focussed on energy-sensing metabolites like AMPK, mTOR, or Sirt1 and considered them as alluring targets to modify the adaptive immune responses in allergic asthma in addition to the other identified catabolic and anabolic pathways. In his studies, he has obtained contradictory results, as well as varied and erratic reactions from the asthmatic patients to the present and potential therapies, which indicated that the knowledge of the pathogenic pathways causing airway allergies is only partially complete. For his studies, the two key main therapeutic targets for asthma identified by him are PPAR-γ and Sirtuin1 or SIRT1.
Peroxisome proliferator-activated receptor gamma, also known as PPAR-γ or Pioglitazone, is a thiazolidinedione-type diabetes medication that stimulates the transcription factor involved in glucose and lipid metabolism. The role of the peroxisome proliferator-activated receptors, PPAR-α and PPAR-γ, in the control of antigen-induced airway inflammation, eosinophil inflow, generation of Th2 cytokines, and AHR in the experimental model of asthma has long been known. It has been found that PPAR activation strongly inhibits the activation of Th2 cells in draining mediastinal lymph nodes and hinders the recruitment of eosinophils in the BALF by stifling dendritic cell’s ability to present antigen, based on the experiments with intratracheal Amarjit Mishra and a group of other talented researchers used GW9662 and other PPAR agonists like ciglitazone to further analyze this finding.
They discovered that treating mice with ovalbumin-induced allergic airway illness with rosiglitazone and pioglitazone had actually reduced bronchial inflammation, airway hyperresponsiveness, ROS generation, and HIF1 levels in lung tissue. Yet, the PPAR-γ activator clinical trials on asthmatic patients produced a range of outcomes. It was discovered that there had been a modest improvement in the airway blockage in a 4-week rosiglitazone therapy study of smokers with asthma and on the late asthmatic reaction in two randomized controlled studies. However, in a randomized 12-week controlled trial, the change in airway reactivity of a sample of obese patients with poorly controlled asthma after pioglitazone medication had revealed its limited efficacy in measures of asthma control. Thus, a few studies on the function of PPAR-γ had already been carried out by various scientists, but Amarjit Mishra’s experimental and qualitative study has revealed that while PPAR-γ has been known to exhibit anti-inflammatory effects of PPAR-γ agonists in preclinical studies, the evaluation of its clinical application indicates the opposite.
Similar to this, Amarjit Mishra has conducted an in-depth study on Sirtuin1 or SIRT1. NAD-dependent deacetylase sirtuin-1, also known as sirtuin1, is recognized as a crucial metabolic sensor that affects the immunological response. In the lungs of asthmatics, there is a decrease in both histone acetyltransferase activity and histone deacetylase activity. Accordingly, studies on the activation of sirtuin1 by synthetic activators like SRT1720 and resveratrol have demonstrated a decrease in the quantity of eosinophil infiltration in lung tissue as well as lower levels of IL-5 and IL-13 cytokines in the BAL fluid of the mice challenged with ovalbumin.
Amarjit Mishra and his team had conducted more trials that were more insightful. It was then demonstrated through in vitro tests using various cell types, including A549 cells, that SIRT1 enhancers like myricetin significantly reduced the TNF—triggered inflammatory response by inhibiting NF-K activation, which in turn resulted in the significantly reduced secretion of pro-inflammatory cytokines, IL6 and IL-8 cytokine. Bergenin, a polyphenolic antitussive and anti-inflammatory biochemical molecule, also increased the TNF-induced pro-inflammatory response by reducing SIRT1 activity. Contrary to SIRT1’s earlier anti-inflammatory function, pharmacological sirtuin suppression has been demonstrated to reduce lung dendritic cell PPAR receptor activity, which in turn reduces allergic inflammation and adaptive Th2 immune response in the mouse model of airway allergy. As a result, Amarjit Mishra’s discovery had improved lung dendritic cell effector function, which in turn produced a pro-Th2 phenotype. According to Amarjit Mishra, sirtuins have a variety of effects on both T cell-dependent inflammations like airway allergies and T cell-independent inflammatory conditions, which are primarily fueled by innate inflammatory mechanisms linked to ageing, oxidative stress, and metabolic dysfunction. This is further explained by the fact that sirtuins are both pro- and anti-inflammatory.
Thus, Amarjit Mishra is working to improve our understanding of the mechanism by which metabolic reprogramming occurs in the case of asthma patients and identify target metabolites for therapeutic intervention for the asthma patients. Such a piece of scientific research is noteworthy. These studies serve as a motivation for other scholars to carry out similar studies and put in light the various contributions that scientists provide to society.