Published ahead of print on October 11, 2004, doi:10.1164/rccm.200406-778OC
Am. J. Respir. Crit. Care Med., Volume 171, Number 1, January 2005, 12-18
A more recent version of this article appeared on January 1, 2005
Submitted on June 22, 2004
Accepted on October 4, 2004
Interleukin-17F Induces Neutrophilia and Amplifies Antigen-induced Allergic Response
Naruhito Oda1, Paola B Canelos1, David M Essayan2, Beverly A Plunkett1, Allen C Myers1, and Shau-Ku Huang1*
1 Johns Hopkins Asthma and Allergy Center, Baltimore, MD, USA,
2 Food and Drug Administration, Rockville, MD, USA
* To whom correspondence should be addressed. E-mail: skhuang{at}jhmi.edu.
IL-17F is a recently described human cytokine belonging to the IL-17 gene family, but its in vivo function remains to be determined. To this end, a full-length mouse IL-17F (mIL-17F) cDNA sequence with a 483-bp coding region sequence was first identified. Pulmonary gene transfer of an IL-17F-expression construct (pcDNAmIL17F) in mice was used to investigate its regulatory role. The results showed first that a significant increase in the number of neutrophils was seen in the bronchoalveolar lavage fluids (BALFs) of IL-17F-transduced mice, concomitant with increased expression of genes encoding C-X-C chemokines and inflammatory cytokines, when compared to mock and PBS controls. Mucosal transfer of IL-17F gene in OVA-sensitized mice prior to Antigen (Ag)-challenge enhanced the levels of Ag-induced pulmonary neutrophilia, but not eosinophilia, goblet cell hyperplasia and mucin gene expression. However, no significant change in the levels of Th2 cytokine expression was noted. A significant enhancement of ventilatory timing in response to inhaled methacholine (Mch) was also seen in IL-17F-transduced, Ag-sensitized mice, while a small, but significant, increase was found in IL-17F-transduced, naive mice. These results suggest a role for IL-17F in the induction of neutrophilia in the lungs and in the exacerbation of Ag-induced pulmonary inflammation.
Key words: cytokine, IL-17F, pulmonary inflammation
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