cerulomycin and Disease-Models--Animal

Caerulomycin A (CRM A) is the first example of natural caerulomycins with a 2,2'-bipyridyl ring core and 6-aldoxime functional group from

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Colorectal Neoplasms; Disease Models, Animal; Gastrointestinal Microbiome; Pyridines; Rats; Rats, Sprague-Dawley

Multiple sclerosis (MS) is a highly detrimental autoimmune disease of the central nervous system. There is no cure for it but the treatment typically focuses on subsiding severity and recurrence of the disease. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS. It is characterized by frequent relapses due to the generation of memory T cells. Caerulomycin A (CaeA) is known to suppress the Th1 cells, Th2 cells, and Th17 cells. Interestingly, it enhances the generation of regulatory T cells (Tregs). Th1 cells and Th17 cells are known to aggravate EAE, whereas Tregs suppress the disease symptoms. Consequently, in the current study we evaluated the influence of CaeA on EAE. Intriguingly, we observed by whole body imaging that CaeA regressed the clinical symptoms of EAE. Further, there was reduction in the pool of Th1 cells, Th17 cells, and CD8 T cells. The mechanism involved in suppressing the EAE symptoms was due to the inhibition in the generation of effector and central memory T cells and induction of the expansion of Tregs. In essence, these findings implicate that CaeA may be considered as a potent future immunosuppressive drug.

Topics: Animals; Biomarkers; Cell Differentiation; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Female; Immunologic Memory; Immunophenotyping; Immunosuppressive Agents; Mice; Multiple Sclerosis; Phenotype; Pyridines; T-Lymphocyte Subsets; T-Lymphocytes

We have recently demonstrated that Caerulomycin A induces regulatory T cells differentiation by suppressing Th1 cells activity. The role of regulatory T cells is well established in suppressing the function of Th2 cells. Th2 cells are known to inflict the induction of the activation of asthma. Consequently, in the present study, we monitored the influence of Caerulomycin A in inhibiting the activity of Th2 cells and its impact in recuperating asthma symptoms. Interestingly, we observed that Caerulomycin A significantly suppressed the differentiation of Th2 cells, as evidenced by downregulation in the GATA-3 expression. Further, decline in the levels of IL-4, IL-5 and IL-13 cytokines and IgE was noted in the animals suffering from asthma. Furthermore, we noticed substantial suppression in the inflammatory response and number of eosinophils in the lungs. In essence, this study signifies an important therapeutic role of Caerulomycin A in asthma.

Topics: Animals; Asthma; Cell Differentiation; Cytokines; Disease Models, Animal; Disease Progression; Eosinophils; Female; GATA3 Transcription Factor; Gene Expression Regulation; Immunoglobulin E; Leukocyte Count; Lung; Lymphocyte Activation; Mice; Pyridines; Severity of Illness Index; Th2 Cells