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ATF3 as an Important Factor of the Acute Phase Lung Inflammatory Response in an Animal Model
Author(s) -
Caruso Carla Romina,
Cabello Noe,
Sinha Utkarshna,
Ekpa Ndifreke,
DiAngelo Susan,
Chroneos Zissis,
Silveyra Patricia
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.444.9
Subject(s) - bronchoalveolar lavage , chemokine , lung , inflammation , immunology , proinflammatory cytokine , activating transcription factor , chemistry , medicine , andrology , transcription factor , biochemistry , gene
Background Ground level ozone, an oxidative photochemical air pollutant, is highly corrosive and once inhaled triggers acute lung inflammation, leading to damage of bronchioles and alveoli, and compromising the innate pulmonary immunity. Our previous research has indicated that the expression of lung pro‐inflammatory chemokines and cytokines, such as Interleukin‐6 (IL‐6), are increased after ozone exposure. Since the activating transcription factor 3 (ATF3) is a known regulator of IL‐6 in other models, in this project we sought to determine whether ATF3, via IL‐6, affects and/or modify the lung acute inflammatory response in an experimental animal model. Methods Male wild type (WT, n=6) and ATF3 knockout (ATF3‐KO, n=5) mice were exposed to 2ppm ozone or filtered air (FA, control) for 3 hours. Lung tissue was collected 4 hours after exposure, and bronchoalveolar lavage fluid (BAL) was obtained 24h post exposure. Total RNA form lung tissue was extracted and retro‐transcribed to measure mRNA levels of IL‐6 by Real Time PCR. Changes in cell counts were evaluated by BAL cytospin analysis, and the expression of the lung injury marker lipocalin‐2 was determined by ELISA in BAL. Results The expression of IL‐6 mRNA was significantly increased by ozone in both WT and KO mice (p<0.05). The lungs of ATF3‐KO mice expressed higher levels of IL‐6 than WT mice, when exposed to FA (10‐fold) or ozone (4‐fold). Moreover, in response to ozone, ATF3‐KO mice expressed significantly higher IL‐6 levels than WT mice (4‐fold, p<0.05). In the BAL, we found an increase in lipocalin‐2 expression in response to ozone, as well as a highly elevated neutrophilic count in ATF3‐KO mice exposed to both FA (23% of total BAL cells) and ozone (40% of total cells) vs. the WT groups (0.2% in FA, 6% in ozone). Conclusion Our preliminary results indicate that ATF3 is an important factor that mediates the lung inflammatory response to acute ozone exposure. This is reflected by the increased levels of acute inflammatory phase cytokines (IL‐6) and cells (neutrophils). Future studies will evaluate the specific mechanisms involved in this response, as well as potential sex differences when including female mice. Support or Funding Information BIRCWH K12HD055882