Exogenous Interleukin-17A Inhibits Eosinophil Differentiation and Alleviates Allergic Airway Inflammation

Abstract

IL-17 is known to play important roles in immune and inflammatory disease, such as in asthma, but its functions in allergic airway inflammation are still controversial, and the molecular mechanisms mediating these functions remain unclear. Increased production of eosinophils in bone marrow and their emergence in the airway have been linked to the onset and progression of allergic asthma. In this study, we investigated the effects of exogenous IL-17 on allergic airway inflammation and explored the underlying molecular mechanisms through eosinophil generation. Exogenous IL-17 significantly attenuated the features of allergic inflammation induced by ovalbumin in mice. It inhibited eosinophil differentiation both in vivo and in vitro, accompanied by down-regulated expression of CC chemokine receptor 3, GATA binding protein 1 (GATA-1), and GATA binding protein 2 (GATA-2), as well as reduced formation of common myeloid progenitors and eosinophil progenitors, but without influencing eosinophil apoptosis. IL-17 also significantly decreased the number of eosinophils in IL-5-transgenic mice, although it notably increased the levels of IL-3, IL-5, and granulocyte/macrophage colony-stimulating factor. In addition, IL-17 had little effect on secretion of the inflammatory cytokines by eosinophils. Neutralization of endogenous IL-17 significantly augmented eosinophil recruitment in the airways. Together, these findings suggest that exogenous IL-17 protects against allergic airway inflammation, most likely through inhibition of the eosinophil differentiation in bone marrow.

Bcl-2 inhibitors reduce steroid-insensitive airway inflammation

“…Mice were immunized intraperitoneally with 100 mL of 20 mg of chicken ovalbumin (OVA; Sigma-Aldrich, St Louis, MO) emulsified in Imject alum (2.25 mg of Al[OH] 3 /2 mg of Mg[OH] 2 ; Thermo Fisher Scientific, Waltham, Mass) on days 0 and 14 (OVA/alum model) 21 or were immunized intraperitoneally at day 0 with 20 mg of grade V chicken egg OVA (Sigma-Aldrich) in endotoxin-free PBS emulsified in 75 mL of complete Freund adjuvant (CFA; Sigma-Aldrich) plus 25 mL of PBS (OVA/CFA model). 22 On days 24, 25, and 26 (OVA/alum) or day 14 (OVA/CFA), mice were challenged with an aerosol of 1% (OVA/alum) or 0.1% (OVA/CFA) OVA in saline for 40 minutes by means of ultrasonic nebulization (DeVilbiss, Somerset, Pa).…”

Rapamycin inhibition of eosinophil differentiation attenuates allergic airway inflammation in mice

“…23 Recently, we also noticed that IL-17 remarkably inhibited eosinophil differentiation in vivo without affecting the levels of IL-5. 24 These studies altogether strongly suggest that targeting inhibition of eosinophil differentiation independent of IL-5 might be an effective approach in controlling allergic airway inflammation.…”

Nanoformulated ABT-199 to effectively target Bcl-2 at mitochondrial membrane alleviates airway inflammation by inducing apoptosis

“…Bronchoalveolar lavage (BAL) fluid and lungs were collected. The OVA/Alum model was established using the eosinophilic airway inflammatory model, as previously reported [26]. …”