Apolipoprotein A-I is an endogenous negative regulator of ovalbumin-induced neutrophilic airway inflammation

Wednesday, October 26, 2011 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center	NHLBI	IMMUNO/INFLAM-4

Authors

• C Dai
• X Yao
• J Lam
• K Keeran
• G Zywicke
• X Qu
• Z Yu
• S Levine

Abstract

Apolipoprotein A-I (apoA-I) is a key component of high-density lipoproteins that mediate reverse cholesterol transport from cells. Here, we investigated whether endogenous apo A-I modulates ovalbumin (OVA)-induced neutrophilic airway inflammation in mice. First, we found that apoA-I expression was significantly reduced in the lungs of OVA-challenged as compared to saline-challenged wild type(WT) C57BL/6 mice. Next, we demonstrated that OVA-challenged apo A-I KO mice had a significant increase in airway neutrophils as compared to OVA-challenged WT mice. Furthermore, OVA-challenged apo A-I KO mice had up-regulated expression of multiple pathways that promote neutrophilic inflammation. These included the up-regulated expression of (i) pro-inflammatory cytokines (IL-17A, TNF), (ii) CXC chemokines and receptors that mediate neutrophil recruitment (CXCL5, CXCR2), (iii) vascular adhesion molecules (VCAM1), and (iv) colony-stimulating factors that prolong neutrophil survival (G-CSF). NF-kB activation was also up-regulated in the lungs of OVA-challenged apoA-I KO mice. We conclude that endogenous apoA-I negatively regulates key pathways that mediate the chemotaxis, vascular adhesion and survival of neutrophils in ovalbumin-induced airway inflammation. This suggests that apo A-I may play an important role in modulating the pathogenesis of airway inflammation in neutrophil-predominant asthma phenotypes.

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