Histone deacetylation of memory T lymphocytes by You-Gui-Wan alleviates allergen-induced eosinophilic airway inflammation in asthma

Research

Hong Ping Zhang^12?, Juan Juan Fu^2?, Tao Fan², Wen Bin Zhang³, Zeng Li Wang⁴, Lei Wang¹² and Gang Wang^12*

• *
  Corresponding author: Gang Wang [email protected]

• ? Equal contributors

Author Affiliations

¹ Pneumology Group, Department of Integrated Traditional Chinese and Western Medicine, State Key Laboratory of Biotherapy of China, West China Hospital, Sichuan University, Chengdu 610041, PR China

² Pneumology Group, Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China

³ Department of Respiratory Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400011, PR China

⁴ Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China

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Chinese Medicine 2015, 10:9 
doi:10.1186/s13020-015-0038-9

Hong Ping Zhang and Juan Juan Fu contributed equally to this work.

Published: 13 May 2015

Abstract (provisional)

Background You-Gui pills (You-Gui-Wan; YGW) can promote T lymphocyte proliferation
and differentiation, and restore Th1/Th2 balance in the treatment of asthma, but their
mechanism of action is not fully known. This study aims to explore whether YGW can
induce histone deacetylation or acetylation in memory T lymphocytes (Tm) for improvement
of airway inflammation in asthma. Methods CD4+CD45RBlow cells, as Tm, were obtained
by magnetic-activated cell sorting and flow cytometry from the spleens of BALB/c mice
with ovalbumin (OVA)-induced asthma. Tm were cocultured with hydrocortisone (CORT;
1000 nM), serum containing low (0.225 g/kg), moderate (0.9 g/kg), or high (3.6 g/kg)
doses of YGW, or medium only, and then adoptively transferred into naïve mice (n?=?5
per group). Recipient mice were challenged with aerosolized OVA. The levels of IL-4,
IL-5, IL-13, and IFN-? in culture supernatants and bronchoalveolar lavage fluid (BALF)
from the OVA-challenged mice were measured by ELISA. Histone deacetylase (HDAC) and
histone acetyltransferase (HAT) activities and protein expressions of T-bet, GATA-3,
and HDAC1–11 in lung tissue were measured by western blotting analyses. The alveolar
eosinophilic inflammation index (AEII) was evaluated in the lungs of adoptive transfer
recipient mice. Results YGW reduced inflammation and eosinophil infiltration into
the lung tissues as evidenced by histology, with similar effects to those of CORT.
High-, moderate-, and low-YGW increased HDAC (P?lt;?0.0001, P?=?0.0009 and P?=?0.0253
respectively) and decreased HAT (P?=?0.0001, P?=?0.0000 and P?=?0.0039, respectively)
activities in dose-dependent manners in the lung tissues of adoptive transfer recipient
mice. Increased histone deacetylation of Tm by YGW reduced the AEII by reducing GATA-3
(P?=?0.014),IL-4 (P?=?0.0004), IL-5 (P?=?0.0067), and IL-13 (P?=?0.0002), and inducing
IFN-? release (P?=?0.0375). Moreover, YGW reduced inflammatory cytokines such as IL-4,
IL-5, and IL-13 by upregulating the activities of HDAC7 (P?=?0.003)/10 (P?=?0.003),
HDAC11 (P?lt;?0.0001), and HDAC9–11 (P?lt;?0.0001, P?lt;?0.0001 and P?lt;?0.0001,
respectively), respectively, and increased IFN-? release by increasing HDAC9 (P?lt;?0.0001).
Conclusions Histone deacetylation of Tm was observed during alleviation of allergen-induced
eosinophilic airway inflammation in asthma by YGW.