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Aspirin‐Triggered Resolvin D1 Protects Against Cytokine Induced Alveolar Epithelial Cell Injury
Author(s) -
Cox Ruan,
Phillips Oluwakemi,
Arias Stephen,
Mandry Maria,
Fukumoto Jutaro,
Cho Young,
Lockey Richard,
Kolliputi Narasaiah
Publication year - 2015
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.29.1_supplement.863.18
Subject(s) - cytokine , medicine , immunology , inflammation , cell adhesion molecule
RATIONALE: Hypercytokinemia is a key hallmark of many acute and chronic lung diseases such as acute respiratory distress syndrome, chronic obstructive pulmonary disease, and asthma. Activation of alveolar epithelial cells by a cytokine storm can lead to increased leukocyte adhesion, further cytokine secretion, enhanced disruption of the alveolar capillary barrier, and ultimately poor gas exchange. Resolution of cytokine induced alveolar epithelial cell activation has not been fully elucidated. Aspirin Triggered Resolution Interaction Phase Product D1 (AT‐RvD1) resolvin reduce inflammation following in vivo systemic administration, however the effects of AT‐RvD1 has not been elucidated and is the focus of this study. METHODS: Human alveolar epithelial cells (hAECs) were pre‐treated with AT‐RvD1 prior to exposure to pro‐inflammatory cytokines IL‐1ß and TNFα. Following cytokine treatment, the ability of AT‐RvD1 to blunt cytokine induced hAEC activation was evaluated. RESULTS: hAECs treated with AT‐RvD1 demonstrated reduced adhesion molecule expression, leukocyte adhesion and pro‐inflammatory cytokine secretion in comparison to cytokine treated controls. In vivo and in vitro analysis revealed a significant decrease in both NFκB and MAP kinase (p38) activity. CONCLUSION: The ability of AT‐RvD1 to blunt the aggressive inflammatory cascade as well halt epithelial cell activation further suggests that it may be a novel treatment strategy for hypercytokinemia. Funding source: This work was funded by the AHA National Scientist Development Grant 09SDG2260957, 14POST18200004, 13PRE17070137 and NIH R01 HL105932 and the Joy McCann Culverhouse Endowment to the Division of Allergy and Immunology.