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Interaction of dendritic cells and T lymphocytes for the therapeutic effect of Dangguiliuhuang decoction to autoimmune diabetes.

Liu T, Cao H, Ji Y, Pei Y, Yu Z, Quan Y, Xiang M - Sci Rep (2015)

Bottom Line: In addition, DGLHD increased α1-antitrypsin (AAT-1), Bcl-2, and CyclinD1, and decreased Bax levels in pancreas, spleen, thymus, DCs, and a NIT-1 cell line, all consistent with protecting and repairing islet β cell.More detailed studies indicated that DGLHD regulated the maturation and function of DCs, decreased the percentage of merocytic dendritic cells (mcDCs) subset, and increased programmed death ligand-1 (PD-L1) expression in DCs.The results demonstrated the reasonable composition of the formula.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

ABSTRACT
In traditional Chinese medicine (TCM), Dangguiliuhuang decoction (DGLHD) is an effective treatment of autoimmune diabetes. Here, we studied potential anti-diabetic mechanisms of DGLHD in a non-obese diabetic (NOD) mouse model. In vitro, DGLHD and individual active ingredients enhanced glucose uptake in HepG2 cells, inhibited T lymphocyte proliferation, and suppressed dendritic cells (DCs) function. In vivo, DGLHD significantly inhibited insulitis, delayed the onset and development of diabetes, promoted insulin secretion and sensitivity, and balanced partially normalized Th1 and Th2 cytokines in NOD mice. In addition, DGLHD increased α1-antitrypsin (AAT-1), Bcl-2, and CyclinD1, and decreased Bax levels in pancreas, spleen, thymus, DCs, and a NIT-1 cell line, all consistent with protecting and repairing islet β cell. More detailed studies indicated that DGLHD regulated the maturation and function of DCs, decreased the percentage of merocytic dendritic cells (mcDCs) subset, and increased programmed death ligand-1 (PD-L1) expression in DCs. DGLHD also impeded T lymphocyte proliferation and promoted regulatory T cells (T(regs)) differentiation in vivo. A JAK2-STAT3-dependent pathway was involved in the suppression by DGLHD of interactions between DCs and T lymphocyte. The experiments implicated five active ingredients in specific anti-diabetic actions of DGLHD. The results demonstrated the reasonable composition of the formula.

No MeSH data available.


Related in: MedlinePlus

DGLHD decreased JAK2, STAT3 protein expression and increased SOCS3 level in the pancreas, spleen and thymus.(A) Respectively western blot results showed the expressions of JAK2, STAT3, p-STAT3 and SOCS3 in 12 week-old NOD mice treated with DGLHD for 4 weeks from 8 until 12 weeks and model control group. β-actin was used as loading control. (B) Bar graphs showed semi-quantitative evaluation of their expression by densitometry. Data were presented as means ± SD (n = 3). *P < 0.05, **P < 0.01 compared with model control group.
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f12: DGLHD decreased JAK2, STAT3 protein expression and increased SOCS3 level in the pancreas, spleen and thymus.(A) Respectively western blot results showed the expressions of JAK2, STAT3, p-STAT3 and SOCS3 in 12 week-old NOD mice treated with DGLHD for 4 weeks from 8 until 12 weeks and model control group. β-actin was used as loading control. (B) Bar graphs showed semi-quantitative evaluation of their expression by densitometry. Data were presented as means ± SD (n = 3). *P < 0.05, **P < 0.01 compared with model control group.

Mentions: To confirm the above results, we measured JAK2, STAT3, and SOCS3 protein levels. The results showed that DGLHD down-regulated the expressions of JAK2, STAT3 and decreased the phosphorylation of STAT3, while up-regulating the inhibitor protein SOCS3 significantly (Fig. 12A,B). The results strongly suggest that inhibiting JAK2-STAT3-dependent signaling pathways in various tissues by DGLHD is involved in its therapeutic actions in this model of NOD.


Interaction of dendritic cells and T lymphocytes for the therapeutic effect of Dangguiliuhuang decoction to autoimmune diabetes.

Liu T, Cao H, Ji Y, Pei Y, Yu Z, Quan Y, Xiang M - Sci Rep (2015)

DGLHD decreased JAK2, STAT3 protein expression and increased SOCS3 level in the pancreas, spleen and thymus.(A) Respectively western blot results showed the expressions of JAK2, STAT3, p-STAT3 and SOCS3 in 12 week-old NOD mice treated with DGLHD for 4 weeks from 8 until 12 weeks and model control group. β-actin was used as loading control. (B) Bar graphs showed semi-quantitative evaluation of their expression by densitometry. Data were presented as means ± SD (n = 3). *P < 0.05, **P < 0.01 compared with model control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4566122&req=5

f12: DGLHD decreased JAK2, STAT3 protein expression and increased SOCS3 level in the pancreas, spleen and thymus.(A) Respectively western blot results showed the expressions of JAK2, STAT3, p-STAT3 and SOCS3 in 12 week-old NOD mice treated with DGLHD for 4 weeks from 8 until 12 weeks and model control group. β-actin was used as loading control. (B) Bar graphs showed semi-quantitative evaluation of their expression by densitometry. Data were presented as means ± SD (n = 3). *P < 0.05, **P < 0.01 compared with model control group.
Mentions: To confirm the above results, we measured JAK2, STAT3, and SOCS3 protein levels. The results showed that DGLHD down-regulated the expressions of JAK2, STAT3 and decreased the phosphorylation of STAT3, while up-regulating the inhibitor protein SOCS3 significantly (Fig. 12A,B). The results strongly suggest that inhibiting JAK2-STAT3-dependent signaling pathways in various tissues by DGLHD is involved in its therapeutic actions in this model of NOD.

Bottom Line: In addition, DGLHD increased α1-antitrypsin (AAT-1), Bcl-2, and CyclinD1, and decreased Bax levels in pancreas, spleen, thymus, DCs, and a NIT-1 cell line, all consistent with protecting and repairing islet β cell.More detailed studies indicated that DGLHD regulated the maturation and function of DCs, decreased the percentage of merocytic dendritic cells (mcDCs) subset, and increased programmed death ligand-1 (PD-L1) expression in DCs.The results demonstrated the reasonable composition of the formula.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

ABSTRACT
In traditional Chinese medicine (TCM), Dangguiliuhuang decoction (DGLHD) is an effective treatment of autoimmune diabetes. Here, we studied potential anti-diabetic mechanisms of DGLHD in a non-obese diabetic (NOD) mouse model. In vitro, DGLHD and individual active ingredients enhanced glucose uptake in HepG2 cells, inhibited T lymphocyte proliferation, and suppressed dendritic cells (DCs) function. In vivo, DGLHD significantly inhibited insulitis, delayed the onset and development of diabetes, promoted insulin secretion and sensitivity, and balanced partially normalized Th1 and Th2 cytokines in NOD mice. In addition, DGLHD increased α1-antitrypsin (AAT-1), Bcl-2, and CyclinD1, and decreased Bax levels in pancreas, spleen, thymus, DCs, and a NIT-1 cell line, all consistent with protecting and repairing islet β cell. More detailed studies indicated that DGLHD regulated the maturation and function of DCs, decreased the percentage of merocytic dendritic cells (mcDCs) subset, and increased programmed death ligand-1 (PD-L1) expression in DCs. DGLHD also impeded T lymphocyte proliferation and promoted regulatory T cells (T(regs)) differentiation in vivo. A JAK2-STAT3-dependent pathway was involved in the suppression by DGLHD of interactions between DCs and T lymphocyte. The experiments implicated five active ingredients in specific anti-diabetic actions of DGLHD. The results demonstrated the reasonable composition of the formula.

No MeSH data available.


Related in: MedlinePlus