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This Article Full Text Full Text (PDF) All Versions of this Article: 292/1/L343    most recent 00030.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Blau, H. Articles by Fabian, I. Search for Related Content PubMed PubMed Citation Articles by Blau, H. Articles by Fabian, I.

Moxifloxacin but not ciprofloxacin or azithromycin selectively inhibits IL-8, IL-6, ERK1/2, JNK, and NF-B activation in a cystic fibrosis epithelial cell line

¹Pulmonary Unit and Graub Cystic Fibrosis Center, Schneider Children's Medical Center of Israel, Petah Tikva; ²Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv; ³Infectious Disease Unit, Schneider Children's Medical Center of Israel, Petah Tikva; and ⁴Pediatric Department, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

Submitted 21 January 2006 ; accepted in final form 18 July 2006

Cystic fibrosis (CF) is associated with severe neutrophilic airway inflammation. We showed that moxifloxacin (MXF) inhibits IL-8 and MAPK activation in monocytic and respiratory epithelial cells. Azithromycin (AZM) and ciprofloxacin (CIP) are used clinically in CF. Thus we now examined effects of MXF, CIP, and AZM directly on CF cells. IB3, a CF bronchial cell line, and corrected C38 cells were treated with TNF-, IL-1, or LPS with or without 5–50 µg/ml MXF, CIP, or AZM. IL-6 and IL-8 secretion (ELISA), MAPKs ERK1/2, JNK, p38, and p65 NF-B (Western blot) activation were measured. Baseline IL-6 was sixfold higher in IB3 than C38 cells but IL-8 was similar. TNF- and IL-1 increased IL-6 and IL-8 12- to 67-fold with higher levels in IB3 than C38 cells post-TNF- (P < 0.05). Levels were unchanged following LPS. Baseline phosphorylated form of ERK1/2 (p-ERK1/2), JNK, and NF-B p65 were higher in IB3 than C38 cells (5-, 1.4-, and 1.4-fold), and following TNF- increased, as did the p-p38, by 1.6- to 2-fold. MXF (5–50 µg/ml) and CIP (50 µg/ml), but not AZM, suppressed IL-6 and IL-8 secretion by up to 69%. MXF inhibited TNF--stimulated MAPKs ERK1/2, 46-kDa JNK, and NF-B up to 60%, 40%, and 40%, respectively. In contrast, MXF did not inhibit p38 activation, implying a highly selective pretranslational effect. In conclusion, TNF- and IL-1 induce an exaggerated inflammatory response in CF airway cells, inhibited by MXF more than by CIP or AZM. Clinical trials are recommended to assess efficacy in CF and other chronic lung diseases.

inflammation; quinolones; immunomodulation; airway epithelium

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