Arsenic trioxide alleviates airway hyperresponsiveness and promotes apoptosis of CD4+ T lymphocytes: evidence for involvement of the ER stress-CHOP pathway.

Abstract

BACKGROUND:

Asthma is a chronic inflammatory disorder of the airway. Arsenic trioxide (ATO) is an ancient Chinese medicine, which is used to treat psoriasis, asthma, and acute promyelocytic leukemia.

AIM:

We wanted to research the effect of arsenic trioxide on asthma.

METHODS:

Using a murine model of asthma, the airway hyperresponsiveness was conducted by the Buxco pulmonary function apparatus. Total cell counts of BALF were counted with a counting chamber. Histopathological analysis of lung tissues was conducted by hematoxylin-eosin or periodic acid-schiff stain. CD4+T cells were purified from the spleen by positive selection, using immunomagnetic beads. Apoptosis measurements were done with Annexin-V/PI staining. Western blot analysis and real time-PCR were performed to assess the expression of C/EBP-homologous protein (CHOP) and glucose-regulated protein 78 (GRP78), respectively. RNA interference was conducted to inhibit the expression of CHOP.

RESULTS:

We found that arsenic trioxide treatment alleviated airway hyperresponsiveness and reduced inflammation of the lung in asthmatic mice. Furthermore, arsenic trioxide treatment promoted apoptosis of CD4+T cells in vivo and in vitro. When CD4+T cells were cultured with arsenic trioxide for 5 h at a concentration of 5 μM, the expression of GRP78 and CHOP was increased. Treatment of CD4+T cells with CHOP siRNA, provided partial resistance to arsenic trioxide-induced apoptosis of CD4+T cells

CONCLUSIONS:

These data demonstrated that arsenic trioxide can reduce the severity of asthma attacks and induce the apoptosis of CD4+ T cell which the ER stress-CHOP pathway involved.

• Authors: K Li, L Zhang, X Xiang, S Gong, L Ma, L Xu, G Wang, Y Liu, X Ji, S Liu, P Chen, H Zeng, J Li
• Journal: Irish journal of medical science (Ir J Med Sci) Vol. 182 Issue 4 Pg. 573-83 (Dec 2013) ISSN: 1863-4362 [Electronic] Ireland
• PMID: 23494705 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Asthmatic Agents
• Anti-Inflammatory Agents
• Arsenicals
• Ddit3 protein, mouse
• Endoplasmic Reticulum Chaperone BiP
• Heat-Shock Proteins
• Hspa5 protein, mouse
• Oxides
• Transcription Factor CHOP
• Arsenic Trioxide

Topics

• Animals
• Anti-Asthmatic Agents (pharmacology)
• Anti-Inflammatory Agents (pharmacology)
• Apoptosis
• Arsenic Trioxide
• Arsenicals (pharmacology)
• Asthma (drug therapy, immunology, physiopathology)
• Bronchial Hyperreactivity (drug therapy, immunology)
• Bronchoalveolar Lavage Fluid (immunology)
• Bronchoconstriction (drug effects)
• CD4-Positive T-Lymphocytes (drug effects, immunology)
• Cells, Cultured
• Disease Models, Animal
• Endoplasmic Reticulum Chaperone BiP
• Endoplasmic Reticulum Stress
• Female
• Heat-Shock Proteins (metabolism)
• Lung (drug effects, immunology)
• Mice
• Mice, Inbred BALB C
• Oxides (pharmacology)
• RNA Interference
• Signal Transduction (drug effects)
• Transcription Factor CHOP (genetics, metabolism)
• Transfection