TNF945; Release Results in Increased Expression of the Innate Immune Regulatory Molecule Surfactant Protein D (SP-D) in a Model of Aspergillus fumigatus (Af) and Ozone-Induced Airway Inflammation

S. Kierstein1, Y. Cao1, X. Yang1, A. Das2, A. Haczku1

Author address: 

1 Pulmonary, Allergy and Critical Care, Universtiy of Pennsylvania, Philadelphia, PA 2 Centocor, King of Prussia, PA

Abstract: 

RATIONALE: TNFα plays a critical role in the initiation of inflammatory changes in the lung by stimulating pro-inflammatory cytokines, chemokines and the subsequent recruitment of inflammatory cells. We have previously shown that SP-D up-regulation is associated with resolution of airway inflammation. Whether there is a regulatory relationship between TNFα and SP-D, is not known. METHODS: The kinetics of TNFα production was evaluated in a murine model of Af sensitization and ozone-induced airway inflammation in wild-type and SP-D deficient mice. Cellular influx and cytokine release were analyzed at different time points between 1-96 hours. SP-D mRNA and protein expression was determined by real time PCR and Western blot. RESULTS: TNFα release peaked 1 h after Af challenge and elevated levels were detected up to 12h. Ozone alone did not significantly increase TNFα , but exacerbated TNFα production in mice 96h after Af provocation. Influx of inflammatory cells was preceded by an increase in IL-4, IL-5, and MIP-1α upon allergen challenge, and IL-6, MIP-1α and TARC following ozone exposure. While MIP-1α and TARC were elevated in SP-D deficient mice, the inflammatory resolution 48h after Af challenge coincided with significant increases of SP-D in wild-type animals. Interestingly, transgenic mice overexpressing TNFα had 4-fold greater SP-D expression in their BAL than control animals. CONCLUSIONS: TNFα release may contribute to up-regulation of SP-D, which in turn facilitates timely resolution of the inflammation. We hypothesize that a negative feedback loop exists involving both TNFα and SP-D to maintain immunological homeostasis in the lung.
2006

abstract No: 

61

Full conference title: 

2006 American Academy of Allergy, Asthma, and Immunology Annual Meeting
    • AAAAI 2006 (62nd)