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Human lung epithelial cells enhanced production of IL‐8, IL‐1β and TNF‐α but not IL‐6 in response to Bacillus anthracis secretory proteins
Author(s) -
Vivekananda Jeevalatha,
Fritz J M.,
Boyd S K.,
Woitaske M D.,
Kiel J L.
Publication year - 2006
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.20.4.a228-a
Subject(s) - bacillus anthracis , secretion , chemokine , tumor necrosis factor alpha , a549 cell , interleukin 8 , immune system , immunology , biology , microbiology and biotechnology , cell culture , in vitro , inflammation , bacteria , biochemistry , genetics
In inhalation anthrax lung is the likely organ exposed to Bacillus anthracis spores. The components of the pulmonary cells are part of the first‐line immune defense within the lung. Recruitment of immune cells such as macrophages and neutrophils to the site of challenge is the primary response of the host to control infection. Interleukin‐8 (IL‐8) is a chemotactic and activating factor for neutrophils which play a pivotal role in host defense mechanisms. To understand the early events of anthrax pathogenesis we choose to use the human lung epithelial cell lines (A549 and H441) as a model system. These cells constitutively synthesize and secrete the chemokine IL‐8. The present study was designed to investigate in vitro the regulatory mechanisms for the expression and production of IL‐8 in anthrax toxins induced toxicity. Our data demonstrates that there is an elevated level of IL‐8 message as well as secreted protein in the media in a time and dose‐dependent manner as determined by RT‐PCR and ELISA. Along with IL‐8, we also observed the up regulation of IL‐1 beta and TNF‐alpha genes. Interestingly our study revealed that there is an inhibition of IL‐6 production, both at the transcriptional and translational level. Finally, the data demonstrates that these activated lung cells spontaneously synthesize a much larger amount of IL‐8 in response to anthrax toxin intoxication thereby potentiating the defense mechanism against infection. This work was sponsored in part by the Department of Defense’s Joint Service Technology Base Program in Chemical and Biological Defense and the Air Force Office of Scientific Research.