Interleukin-17F induces pulmonary neutrophilia and amplifies antigen-induced allergic response.
Interleukin (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 cDNA sequence with a 483-bp coding region sequence was first identified. Pulmonary gene transfer of an IL-17F expression construct (pcDNAmIL-17F) 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 of IL-17F-transduced mice, concomitant with increased expression of genes encoding C-X-C chemokines and inflammatory cytokines when compared with mock and phosphate-buffered saline control animals. Mucosal transfer of the IL-17F gene in ovalbumin (OVA)-sensitized mice before 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 was also seen in IL-17F-transduced, Ag-sensitized mice, whereas 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.
Oda
Naruhito
N
Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA.
Canelos
Paola B
PB
Essayan
David M
DM
Plunkett
Beverly A
BA
Myers
Allen C
AC
Huang
Shau-Ku
SK
D000485:Allergens; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001980:Bronchi / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology*; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D007249:Inflammation; D020381:Interleukin-17 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000473:pathology*; D010047:Ovalbumin / Q000276:immunology; D010993:Plethysmography, Whole Body; D012119:Respiration; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D014161:Transduction, Genetic; D015854:Up-Regulation
D000485:Allergens; D018925:Chemokines; D016207:Cytokines; D020381:Interleukin-17; D010047:Ovalbumin