BJ-1108, a 6-Amino-2,4,5-trimethylpyridin-3-ol analogue, regulates differentiation of Th1 and Th17 cells to ameliorate experimental autoimmune encephalomyelitis

Abstract

BackgroundCD4+ T cells play an important role in the initiation of an immune response by providing help to other cells. Among the helper T subsets, interferon-γ (IFN-γ)-secreting T helper 1 (Th1) and IL-17-secreting T helper 17 (Th17) cells are indispensable for clearance of intracellular as well as extracellular pathogens. However, Th1 and Th17 cells are also associated with pathogenesis and contribute to the progression of multiple inflammatory conditions and autoimmune diseases.ResultsIn the current study, we found that BJ-1108, a 6-aminopyridin-3-ol analogue, significantly inhibited Th1 and Th17 differentiation in vitro in a concentration-dependent manner, with no effect on proliferation or apoptosis of activated T cells. Moreover, BJ-1108 inhibited differentiation of Th1 and Th17 cells in ovalbumin (OVA)-specific OT II mice. A complete Freund’s adjuvant (CFA)/OVA-induced inflammatory model revealed that BJ-1108 can reduce generation of proinflammatory Th1 and Th17 cells. Furthermore, in vivo studies showed that BJ-1108 delayed onset of disease and suppressed experimental autoimmune encephalomyelitis (EAE) disease progression by inhibiting differentiation of Th1 and Th17 cells.ConclusionsBJ-1108 treatment ameliorates inflammation and EAE by inhibiting Th1 and Th17 cells differentiation. Our findings suggest that BJ-1108 is a promising novel therapeutic agent for the treatment of inflammation and autoimmune disease.

Amelioration of Experimental autoimmune encephalomyelitis and DSS induced colitis by NTG-A-009 through the inhibition of Th1 and Th17 cells differentiation

“…Antigen presenting cells like macrophages, microglia, and astrocytes play an important role in the pathogenesis and progression of EAE by presenting myelin epitopes to autoreactive T cells 37 , 58 . IFN-γ and IL-17 enhance the expression of MHC-II, macrophage activation and trafficking of leukocyte in to CNS 59 – 61 .…”

Synthesis of Pyridoxine-Derived Dimethylpyridinols Fused with Aminooxazole, Aminoimidazole, and Aminopyrrole

“…Our previous synthetic strategies for lead compound discovery are summarized and illustrated in Figure 1 [ 12 , 13 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. Using an amine group of 2 at C(6)-position as a synthetic handle, amidopyridinols 3 and ureido-/thioureido-/carbamato-pyridinols 4 have been synthesized to generate a diverse set of compound collections [ 23 , 24 , 25 , 26 , 27 ].…”

BJ‐2266 ameliorates experimental autoimmune encephalomyelitis through down‐regulation of the JAK/STAT signaling pathway

“…Highly efficient and practical synthetic methods starting from vitamin B 6 which have been developed by us were used for the preparation of the pyridinol derivatives. Along with the construction of chemical library of this unique skeleton, biological studies have been extensively and intensively performed on the effect of pyridinols against reactive oxygen species, angiogenesis, cancer, inflammatory bowel disease, autoimmune disease, and so forth . Based on the previous data obtained from diverse biological evaluation of the pyridinols, we picked out two hundred pyridinol derivatives from the compound library to check their effect on T‐cell differentiation and function.…”