A fungal metabolite with antifungal and immunosuppressant activities
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Caerulomycin A is an fungal metabolite originally isolated from Actinoalloteichus with antifungal and immunosuppressant activites.1,2,3,4 It inhibits the growth of C. albicans, C. glabrata, and C. krusei (MICs = 0.78-1.56, 0.39-0.78, and 0.78-1.56 μg/ml, respectively).1 Caerulomycin A induces expansion of CD4+Foxp3+ regulatory T cells (Tregs) and decreases the number of Th1 and T17 cells in vitro via increased TGF-β-mediated Smad3 activity and reduces IFN-γ-induced STAT1 signaling.2 In vivo, caerulomycin A (10 mg/kg) reduces IL-6, TNF-α, and IFN-γ production, inflammation, and synovitis in a mouse model of collagen-induced arthritis. Caerulomycin A suppresses the differentiation of Th2 cells and reduces levels of IL-4, IL-5, IL-13, and IgE and eosinophil lung infiltration in a mouse model of ovalbumin-induced asthma.3 It also increases production of Tregs, reduces production of Th1, Th17, and CD8 T cells, and reduces disease severity in a mouse model of experimental autoimmune encephalomyelitis (EAE).4
1.Ambavane, V., Tokdar, P., Parab, R., et al.Caerulomycin A - An antifungal compound isolated from marine actinomycetesAdv. Microbiol.4(9)567-578(2014) 2.Gurram, R.K., Kujur, W., Maurya, S.K., et al.Caerulomycin A enhances transforming growth factor-β (TGF-β)-Smad3 protein signaling by suppressing interferon-γ (IFN-γ)-signal transducer and activator of transcription 1 (STAT1) protein signaling to expand regulatory T cells (Tregs)J. Biol. Chem.289(25)17515-17528(2014) 3.Kujur, W., Gurram, R.K., Haleem, N., et al.Caerulomycin A inhibits Th2 cell activity: A possible role in the management of asthmaSci. Rep.515396(2015) 4.Kujur, W., Gurram, R.K., Maurya, S.K., et al.Caerulomycin A suppresses the differentiation of na?ve T cells and alleviates the symptoms of experimental autoimmune encephalomyelitisAutoimmunity50(5)317-328(2017)
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