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THE EFFECTS OF ANTI-INFLAMMATORY IFNγ AND PRO-INFLAMMATORY TNFα, IL-1β ON CHEMOKINE RELEASE IN MOUSE EPITHELIAL CELLS
Citation:
MANZO, N., J. E. RICHARDS, R. SLADE, L. D. Martin, AND J. A. DYE. THE EFFECTS OF ANTI-INFLAMMATORY IFNγ AND PRO-INFLAMMATORY TNFα, IL-1β ON CHEMOKINE RELEASE IN MOUSE EPITHELIAL CELLS. Presented at American Thoracic Society 2008 International Conference, Toronto, ON, CANADA, May 16 - 21, 2008.
Impact/Purpose:
Asthma is a chronic inflammatory disorder of the airways that can be aggravated by air pollution. The airway inflammation consists of complex interactions of pro-inflammatory and anti-inflammatory mediators. This abstracts describes the interactions of pro- and anti-inflammatory mediators in lungs cells and provides a basis for the development of an in vitro model to evaluate the effects of air pollutants on inflammatory airway diseases.
Description:
RATIONALE: Asthma is a chronic inflammatory disorder of the airways that affects nearly 20 million individuals in the US. Airway inflammation is a hallmark characteristic of asthma and is the result of numerous pro-inflammatory cytokines such as IL-1β and TNFα . Interestingly, the anti-inflammatory TH1 cytokine IFNγ is also present in the asthmatic airways. The role of IFNγ , when present with pro-inflammatory cytokines like TNFα and IL-1β , is uncertain. It is our hypothesis that epithelial exposure to IL-1β and TNFα , individually, or in combination, will stimulate increases in the chemokines MIP-2 and RANTES, the effects of which will be decreased during co-exposure with IFNγ . METHODS: Two different mouse cells characteristic of different lung regions were employed: (1) primary mouse tracheal epithelial cells grown at an air-liquid interface characteristic of the conducting airways, and (2) the LA-4 cell line characteristic of alveolar type II cells. Cells were exposed to differing combinations of TNFα , IL-1β , and IFNγ (2ng/mL) for 24hrs. Supernatants and cell lysates were collected and analyzed for release of MIP-2 and RANTES by ELISA. Cytotoxicity was inferred by the release of lactate dehydrogenase. RESULTS: In both cell types, exposure to either IL-1β or TNFα , individually and in combination, resulted in increased release of MIP-2 and RANTES. Unexpectedly, co-exposure of IL-1β and TNFα with IFNγ potentiated and prolonged RANTES release in a cell type specific manner. CONCLUSIONS: In the presence of IL-1β and TNFα, IFNγ elicited a net pro-inflammatory effecter cell response (i.e., increased MIP-2 and RANTES release) from mouse airway epithelial cells. Seemingly, while IFNγ can function to diminish inflammatory responses in asthmatics, under certain conditions, it may also serve to perpetuate inflammatory processes.