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Microrna-203 Regulates Aryl Hydrocarbon Receptor in Cockroach Mediated Allergic Responses
Sunday, March 6, 2016: 4:45 PM
Concourse Foyer (Convention Center)
Yilin Zhao, PhD, Lipeng Qiu, PhD, Danh Do, PhD, Heng Wang, MD PhD, Xiaopeng Liu, PhD, Peisong Gao, MD PhD
Rationale: Aryl Hydrocarbon Receptor (AhR) is a multifunctional regulator that responds to environmental stimuli and plays a role in normal cell development and immune regulation. Our findings suggest that AhR controls mast cell homeostasis and cockroach allergen (CRE)-induced immune responses. microRNA (miR)-203 was predicted to target AhR and shown to be down-regulated in asthma. We sought to investigate whether miR-203 can target AhR and regulate AhR-mediated allergic responses. 

Methods:  miR-203 expression was detected in lung tissues from CRE-challenged mouse model of asthma by qRT-PCR. Levels of miR-203, AhR, and its downstream targets were examined in CRE-treated A549 cells, an alveolar epithelial cell line. AhR regulation by miR-203 in CRE-treated A549 and anti-ovalbumin (OVA) IgE sensitized bone marrow-derived mast cells (BMMCs) was also investigated.

Results: Expression of miR-203 was significantly reduced in lung tissues of CRE-induced mouse model of asthma compared to un-challenged controls. The levels of miR-203 in CRE-treated A549 cells were also reduced. Conversely, the expression of AhR and its downstream targets (i.e., arnt, cyp1a1, COX2) was increased in these cells. AhR expression was remarkably inhibited in A549 after transfection with miR-203 mimics at both the mRNA and protein levels. Furthermore, COX2, an implicated target of AhR, was also significantly down-regulated.  Kynurenine (KYN), an AhR agonist, potentiates IgE-mediated mast cell degranulation as determined by the release of β-hexosaminidase, which was significantly suppressed in miR-203 over-expressed BMMCs.

Conclusions: These results suggest that miR-203 may inhibit AhR expression and play a role in regulating AhR-mediated responses in allergic diseases like asthma.